KR102525213B1 - Identifiable quick response(qr)-coded orodispersible films, and preparation method thereof using 3d printer - Google Patents
Identifiable quick response(qr)-coded orodispersible films, and preparation method thereof using 3d printer Download PDFInfo
- Publication number
- KR102525213B1 KR102525213B1 KR1020210004700A KR20210004700A KR102525213B1 KR 102525213 B1 KR102525213 B1 KR 102525213B1 KR 1020210004700 A KR1020210004700 A KR 1020210004700A KR 20210004700 A KR20210004700 A KR 20210004700A KR 102525213 B1 KR102525213 B1 KR 102525213B1
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- KR
- South Korea
- Prior art keywords
- poloxamer
- code
- film
- drug
- oral disintegrating
- Prior art date
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- 238000002360 preparation method Methods 0.000 title description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims abstract description 94
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 81
- 229920001983 poloxamer Polymers 0.000 claims abstract description 80
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- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 claims abstract description 36
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Abstract
본 발명은 QR 코드가 적용된 구강붕해필름 및 3D 프린팅 기술을 이용하여 이를 제조하는 방법에 관한 것으로, 상세하게는 아리피프라졸(aripiprazole), 팔리페리돈(paliperidone) 또는 팔리페리돈 팔미테이트(paliperidone palmitate)에서 선택되는 항정신제 약물, 필름 형성제로서 폴리에틸렌옥사이드, 가용화제로서 폴록사머, 및 산도조절제로서 시트릭산을 포함하며, 환자 정보, 약물 정보 또는 상기 정보가 포함된 인터넷상 파일 주소(URL)를 포함하는 QR 코드가 표지된 것을 특징으로 하는 QR 코드가 적용된 구강붕해필름 및 이의 제조방법을 제공한다.
본 발명에 따른 QR 코드가 적용된 구강붕해필름은 3D 프린터를 이용하여 쉽고 간단하게 제조할 수 있으며, 스마트폰 등을 통해 상기 구강붕해필름에 적용된 QR 코드를 스캔함으로써 환자 및 약물에 대한 정보를 쉽게 파악할 수 있다.The present invention relates to an oral disintegrating film to which a QR code is applied and a method for manufacturing the same using 3D printing technology, and in detail, selected from aripiprazole, paliperidone or paliperidone palmitate Contains an antipsychotic drug, polyethylene oxide as a film former, poloxamer as a solubilizer, and citric acid as an acidity regulator, including patient information, drug information, or a file address (URL) on the Internet containing the information It provides an oral disintegrating film to which a QR code is applied, characterized in that the QR code is marked, and a manufacturing method thereof.
The oral disintegrating film to which the QR code is applied according to the present invention can be easily and simply manufactured using a 3D printer, and information on patients and drugs can be obtained by scanning the QR code applied to the orally disintegrating film through a smartphone or the like. Easy to figure out.
Description
본 발명은 QR 코드가 적용된 구강붕해필름 및 3D 프린팅 기술을 이용하여 이를 제조하는 방법에 관한 것이다.The present invention relates to an oral disintegrating film to which a QR code is applied and a method for manufacturing the same using 3D printing technology.
삼차원(3dimension, 3D) 프린터는 설계 데이터에 따라 액체 또는 파우더 형태의 폴리머(수지), 금속 등의 재료를 가공·적층방식(layer-by-layer)으로 쌓아올려 입체물을 제조하는 장비이다. 이는 삼차원 그래픽 응용프로그램에 따라 생산하고자 하는 형상을 레이저와 파우더 재료를 활용하여 신속 조형하는 기술을 의미하는 RP(rapid prototyping)에서 유래되었다. 입체 형상의 재료를 기계가공 또는 레이저를 이용하여 자르거나 깎는 방식으로 입체물을 생산하는 절삭가공(subtractive manufacturing)과 반대되는 개념이다.A three-dimensional (3D) printer is an equipment that manufactures three-dimensional objects by stacking materials such as liquid or powdery polymers (resin) and metals in a layer-by-layer manner according to design data. This is derived from RP (rapid prototyping), which refers to a technology of rapid prototyping using laser and powder materials to produce shapes according to 3D graphics applications. It is the opposite concept of subtractive manufacturing, which produces three-dimensional objects by cutting or shaving three-dimensional materials using mechanical processing or lasers.
일반적으로 인쇄를 통해 제품을 입체적으로 만드는 삼차원 프린터는 방식에 따라 액체 기반의 방식인 SLA(stereolithography)와 파우더 기반 방식인 SLS(selective laser sintering), 그리고 고체 기반 방식인 FDM(fused deposition modeling, 용융 침착 모델링 방식)이 있다.In general, 3D printers that make a product three-dimensional through printing are liquid-based, SLA (stereolithography), powder-based, SLS (selective laser sintering), and solid-based, FDM (fused deposition modeling), depending on the method. modeling method).
아리피프라졸(aripiprazole)은 7-{4-[4-(2,3-디클로로페닐)피페라진-1-일]부톡시}-3,4-디하이드로퀴놀린-2(1H)-원 (7-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one)의 IUPAC명(IUPAC name)으로 명명되는 의약용 화합물이다. 아리피프라졸은 도파민 작용성 신경전달물질 길항제로서, 정신분열증(schizophrenia), 양극성 장애(bipolar disorder), 임상우울증(clinical depression) 등의 치료에 사용되는 비전형 항정신제 및 항우울제로서 사용될 수 있는 카보스트릴 유도체(carbostyril derivatives)의 일종이다.Aripiprazole is 7-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one (7-{ It is a pharmaceutical compound named by the IUPAC name of 4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one). Aripiprazole is a dopaminergic neurotransmitter antagonist, a carbostril derivative that can be used as an atypical antipsychotic and antidepressant used in the treatment of schizophrenia, bipolar disorder, clinical depression, etc. (carbostyril derivatives).
아리피프라졸은 정제 형태의 제형으로서 널리 시판되고 있지만(Abilify™, Otsuka Pharmaceutical Co), 더 성공적인 정신분열증 치료를 위해 삼키는 형태의 정제나 경구 용액(oral solution) 같은 제형보다 더 손쉬운 형태의 복용 제형이 선호되고 있다.Aripiprazole is widely marketed as a formulation in tablet form (Abilify™, Otsuka Pharmaceutical Co), but for more successful treatment of schizophrenia, a more convenient dosage form is preferred over formulations such as swallowed tablets or oral solutions. there is.
또한, 일반적인 의약품의 경우 환자에 대한 정보 및 약물에 대한 용법, 용량 및 여러 정보들은 포장지에 기재를 하여 환자에게 정보를 제공하고 있는데, 항정신성 약제나 마약류는 의사와 약사 측면에서는 관리와 처방이 중요하고, 환자측면에서는 복용을 하는 것이 중요하며, 환자의 복약 순응도를 관리하기 위해서 의사, 약사, 환자간의 정보 교류 또한 중요하기에, 이를 보다 효과적으로 관리할 수 있는 방법이 필요한 실정이다.In addition, in the case of general medicines, information about the patient, usage, dosage, and various information about the drug are written on the packaging to provide information to the patient. And, from the patient's point of view, it is important to take medications, and information exchange between doctors, pharmacists, and patients is also important in order to manage the patient's medication compliance, so a method for managing this more effectively is needed.
본 발명의 목적은 항정신제 약물을 포함하며, 환자 및 약물에 대한 정보 관리가 효과적인 약물 제형 및 이의 제조 방법을 제공하는 데에 있다.An object of the present invention is to provide a drug formulation containing an antipsychotic drug and effective in managing information on patients and drugs, and a method for preparing the same.
본 발명은 아리피프라졸(aripiprazole), 팔리페리돈(paliperidone) 또는 팔리페리돈 팔미테이트(paliperidone palmitate)에서 선택되는 항정신제 약물, 필름 형성제로서 폴리에틸렌옥사이드, 가용화제로서 폴록사머, 및 산도조절제로서 시트릭산을 포함하며, 환자 정보, 약물 정보 또는 상기 정보가 포함된 인터넷상 파일 주소(URL)를 포함하는 QR 코드가 표지된 것을 특징으로 하는 QR 코드가 적용된 구강붕해필름을 제공한다.The present invention is an antipsychotic drug selected from aripiprazole, paliperidone or paliperidone palmitate, polyethylene oxide as a film former, poloxamer as a solubilizer, and citric acid as an acidity regulator. Including, provides an oral disintegrating film to which the QR code is applied, characterized in that the QR code containing patient information, drug information or a file address (URL) on the Internet containing the information is marked.
본 발명은 아리피프라졸(aripiprazole), 팔리페리돈(paliperidone) 또는 팔리페리돈 팔미테이트(paliperidone palmitate)에서 선택되는 항정신제 약물, 필름 형성제로서 폴리에틸렌옥사이드, 가용화제로서 폴록사머, 및 산도조절제로서 시트릭산을 혼합하여 혼합물을 제조하는 단계; 및 상기 제조된 혼합물을 3D 프린터 압출기에 로딩하고 용융·압출시켜 구강붕해필름을 형성하며, 이와 동시에 환자 정보, 약물 정보 또는 상기 정보가 포함된 인터넷상 파일 주소(URL)를 포함하는 QR 코드를 상기 구강붕해필름 상에 생성하는 단계;를 포함하는 QR 코드가 적용된 구강붕해필름 제조방법 및 이에 따라 제조된 QR 코드가 적용된 구강붕해필름을 제공한다.The present invention is an antipsychotic drug selected from aripiprazole, paliperidone or paliperidone palmitate, polyethylene oxide as a film former, poloxamer as a solubilizer, and citric acid as an acidity regulator. mixing to prepare a mixture; And the prepared mixture is loaded into a 3D printer extruder and melted and extruded to form an oral disintegrating film, and at the same time, a QR code including patient information, drug information, or a file address (URL) on the Internet containing the information A method for manufacturing an oral disintegrating film to which a QR code is applied and an oral disintegrating film to which a QR code manufactured according to the method is applied are provided.
본 발명에 따른 QR 코드가 적용된 구강붕해필름은 3D 프린터를 이용하여 쉽고 간단하게 제조할 수 있으며, 필름 형성제, 가용화제 및 산도조절제의 최적 함량 및 최적 제조 조건에 따라 제조됨으로써 상기 구강붕해필름은 구강붕해속도가 우수하고 용해도가 향상되어 빠른 용출로 약물 전달에 효과적이다.The oral disintegrating film to which the QR code is applied according to the present invention can be easily and simply manufactured using a 3D printer, and is manufactured according to the optimal content and optimal manufacturing conditions of the film forming agent, solubilizer and acidity regulator, thereby achieving the oral disintegration The film has excellent oral disintegration rate and improved solubility, so it is effective for drug delivery with rapid dissolution.
또한, 스마트폰 등을 통해 상기 구강붕해필름에 적용된 QR 코드를 스캔함으로써 환자 및 약물에 대한 정보를 쉽게 파악할 수 있고, 이에 따른 적절한 복용을 통해 복약 순응도와 신뢰도를 높여 효과적으로 질환을 치료할 수 있으며, 따로 관리가 필요한 의약품을 체계적으로 관리할 수 있다.In addition, by scanning the QR code applied to the oral disintegrating film through a smartphone, etc., information on patients and drugs can be easily grasped, and medication compliance and reliability can be effectively treated by appropriate intake accordingly, Drugs that require separate management can be systematically managed.
도 1은 본 발명의 일 실시예에 따른 QR 코드가 적용된 구강붕해필름(QRODF)의 제조 방법과 이의 활용 형태를 개략적으로 나타낸 것이다.
도 2는 본 발명의 일 실험예에 따른 필름 표면의 주사전자현미경 이미지이다.
도 3은 본 발명의 일 실험예에 따른 필름의 인장강도를 측정한 결과 그래프이다.
도 4는 본 발명의 일 실험예에 따라 수행된 시차 주사 열량 분석 결과이다.
도 5는 본 발명의 일 실험예에 따라 수행된 X-선 회절 분석 결과이다.
도 6은 본 발명의 일 실험예에 따른 구강붕해필름의 약물 방출 정도를 평가한 결과이다.
도 7은 본 발명의 일 실시예에 따라 제조된 QRODF 이미지로, (A)는 QRODF, (B)는 QRODF의 접힘, (C)는 QR코드를 스캔한 스마트폰의 스크린샷을 나타낸 것이다.
도 8은 본 발명의 일 실시예에 따라 제조된 QRODF 이미지로, (A)는 QRODF와 스마트폰 카메라를 이용한 QR 코드 인식을, (B)는 QR코드에 담긴 정보를 나타낸 스마트폰의 스크린샷을 나타낸 것이다.
도 9는 본 발명의 일 실시예에 따라 제조된 QRODF 이미지로, (A)는 QRODF와 스마트폰 카메라를 이용한 QR 코드 인식을, (B)는 QR코드에 담긴 URL 정보를 나타낸 스마트폰의 스크린샷, (C)는 해당 링크 터치 후 접속되는 웹페이지의 스마트폰 스크린샷을 나타낸 것이다.1 schematically shows a method of manufacturing an oral disintegrating film (QRODF) to which a QR code is applied and a form of use thereof according to an embodiment of the present invention.
2 is a scanning electron microscope image of the surface of a film according to an experimental example of the present invention.
Figure 3 is a graph of the results of measuring the tensile strength of the film according to an experimental example of the present invention.
4 is a differential scanning calorimetry analysis result performed according to an experimental example of the present invention.
5 is an X-ray diffraction analysis result performed according to an experimental example of the present invention.
6 is a result of evaluating the degree of drug release of an oral disintegrating film according to an experimental example of the present invention.
7 is a QRODF image manufactured according to an embodiment of the present invention, (A) is a QRODF, (B) is a folding of a QRODF, and (C) shows a screen shot of a smartphone scanning a QR code.
8 is a QRODF image manufactured according to an embodiment of the present invention, (A) is a QR code recognition using a QRODF and a smartphone camera, and (B) is a screenshot of a smartphone showing information contained in a QR code. it is shown
9 is a QRODF image manufactured according to an embodiment of the present invention, (A) is a screenshot of a smartphone showing QR code recognition using QRODF and a smartphone camera, and (B) is URL information contained in a QR code. , (C) shows a smartphone screen shot of the webpage accessed after touching the corresponding link.
이하, 본 발명을 상세하게 설명하기로 한다.Hereinafter, the present invention will be described in detail.
본 발명은 항정신제 약물, 필름 형성제, 가용화제, 및 산도조절제를 포함하며, 환자 정보, 약물 정보 또는 상기 정보가 포함된 인터넷상 파일 주소(URL)를 포함하는 QR 코드가 표지된 것을 특징으로 하는, QR 코드가 적용된 구강붕해필름을 제공한다.The present invention includes an antipsychotic drug, a film former, a solubilizer, and an acidity regulator, and is marked with a QR code including patient information, drug information, or a file address (URL) on the Internet containing the information. To provide an oral disintegrating film to which a QR code is applied.
상기 항정신제 약물은 정신병 치료에 쓰이는 향정신 약제의 일종으로, 아리피프라졸(aripiprazole), 팔리페리돈(paliperidone), 팔리페리돈 팔미테이트(paliperidone palmitate), 리스페리돈(risperidone), 브렉스피프라졸(brexpiprazole), 할로페리돌(haloperidol), 클로자핀(clozapine), 쿠에티아핀(quetiapine), 올란자핀(olanzapine) 등을 포함할 수 있고, 바람직하게는 아리피프라졸(aripiprazole), 팔리페리돈(paliperidone), 또는 팔리페리돈 팔미테이트(paliperidone palmitate)일 수 있으나, 이에 제한되는 것은 아니다.The antipsychotic drug is a type of psychotropic drug used for the treatment of psychosis, and includes aripiprazole, paliperidone, paliperidone palmitate, risperidone, brexpiprazole, may include haloperidol, clozapine, quetiapine, olanzapine, etc., preferably aripiprazole, paliperidone, or paliperidone palmitate palmitate), but is not limited thereto.
이 외에도 다양한 펩타이드나 단백질 의약품 등을 포함할 수 있다.In addition to this, various peptide or protein drugs may be included.
하기 표 1은 본 발명의 일 실시예에 사용된 항정신제 약물인 아리피프라졸의 물리화학적 특성을 나타낸 것이다.Table 1 below shows the physicochemical properties of aripiprazole, an antipsychotic drug used in an embodiment of the present invention.
상기 필름 형성제는 수용성 중합체로, 구강 내 타액에 의해 제제의 붕해가 일어나며, 핫멜트 방식의 3D 프린팅으로 필름 형성이 가능한 제제가 선택될 수 있다. The film-forming agent is a water-soluble polymer, and the disintegration of the formulation occurs by saliva in the oral cavity, and a formulation capable of forming a film by hot-
바람직하게는, 폴리에틸렌옥사이드(polyethylene oxide, PEO)일 수 있으며, 보다 바람직하게는 100,000 Da 이상의 분자량을 가지고 녹는점이 65-68℃인 폴리에틸렌옥사이드 N10이 필름 형성제로 유용하게 사용될 수 있다.Preferably, it may be polyethylene oxide (PEO), and more preferably, polyethylene oxide N10 having a molecular weight of 100,000 Da or more and a melting point of 65-68 ° C can be usefully used as a film forming agent.
이 외에도, 하이드록시프로필셀룰로오스(hydroxypropylcellulose, HPC), 하이드록시프로필메틸셀룰로오스(hydroxypropyl methylcellulose, HPMC)와 같은 셀룰로오스 유도체, 폴리비닐알코올(poly vinyl alcohol, PVA), 폴리비닐 피롤리돈 (poly vinyl pyrrolidone, PVP) 등이 포함될 수 있으나, 이에 제한되지 않고, 핫멜트 방식의 3D 프린팅으로 필름 형성이 가능한 고분자류가 모두 포함될 수 있다.In addition to this, cellulose derivatives such as hydroxypropylcellulose (HPC) and hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA), polyvinyl pyrrolidone, PVP) may be included, but is not limited thereto, and all polymers capable of forming a film by
상기 가용화제는 잘 용해되지 않는 아리피프라졸과 같은 상기 약물의 용해도를 향상시키기 위해 사용되는 제제로 계면활성제가 선택될 수 있다.As the solubilizing agent, a surfactant may be selected as an agent used to improve the solubility of the drug, such as aripiprazole, which is poorly soluble.
바람직하게는, 폴록사머(poloxamer)와 같이 비이온성 계면 활성제, 예를 들어, 폴록사머 101, 폴록사머 105, 폴록사머 108, 폴록사머 122, 폴록사머 123, 폴록사머 124, 폴록사머 181, 폴록사머 182, 폴록사머 183, 폴록사머 184, 폴록사머 185, 폴록사머 188, 폴록사머 212, 폴록사머 215, 폴록사머 217, 폴록사머 231, 폴록사머 234, 폴록사머 235, 폴록사머 237, 폴록사머 238, 폴록사머 282, 폴록사머 284, 폴록사머 288, 폴록사머 331, 폴록사머 333, 폴록사머 334, 폴록사머 335, 폴록사머 338, 폴록사머 401, 폴록사머 402, 폴록사머 403, 폴록사머 407 등에서 선택될 수 있으며, 보다 바람직하게는 폴록사머 188일 수 있으나, 이에 제한되는 것은 아니다.Preferably, a non-ionic surfactant such as a poloxamer, for example, poloxamer 101, poloxamer 105, poloxamer 108, poloxamer 122, poloxamer 123, poloxamer 124, poloxamer 181, poloxamer 182, poloxamer 183, poloxamer 184, poloxamer 185, poloxamer 188, poloxamer 212, poloxamer 215, poloxamer 217, poloxamer 231, poloxamer 234, poloxamer 235, poloxamer 237, poloxamer 238, poloxamer 282, poloxamer 284, poloxamer 288, poloxamer 331, poloxamer 333, poloxamer 334, poloxamer 335, poloxamer 338, poloxamer 401, poloxamer 402, poloxamer 403, poloxamer 407, etc. It may be, more preferably poloxamer 188, but is not limited thereto.
상기 폴록사머는 상기 폴리에틸렌옥사이드 100 중량부에 대하여, 10 중량부 포함될 수 있다. 상기 폴록사머의 함량이 10 중량부를 초과하면 점도가 과다하게 낮아지게 되어 필름의 형성을 저해하고 제조된 필름의 물성을 저하시키게 된다. 또한, 폴록사머의 함량이 10 중량부 미만인 경우 본 발명에서 의도하고자 하는 구강붕해필름을 제조할 수 없는 문제점이 있다. The poloxamer may be included in 10 parts by weight based on 100 parts by weight of the polyethylene oxide. When the content of the poloxamer exceeds 10 parts by weight, the viscosity is excessively lowered, thereby inhibiting film formation and deteriorating physical properties of the produced film. In addition, when the content of poloxamer is less than 10 parts by weight, there is a problem in that the oral disintegrating film intended in the present invention cannot be prepared.
본 발명의 일 실험예에 따르면, 폴리에틸렌옥사이드 N10 100 중량부에 폴록사머 188이 10 중량부로 포함될 때, 필름의 표면이 균일하고 매끄럽게 형성되었으며, 높은 인장강도를 나타냄을 확인할 수 있다.According to an experimental example of the present invention, when 10 parts by weight of poloxamer 188 is included in 100 parts by weight of polyethylene oxide N10, it can be confirmed that the surface of the film is formed uniformly and smoothly, and exhibits high tensile strength.
또한, 적정한 양의 폴록사머는 구강붕해필름에 유연성을 부여할 수 있다. In addition, an appropriate amount of poloxamer can impart flexibility to the oral disintegrating film.
이 외에도 적합한 보조가용화제로서, 솔루플러스(soluplus), 폴리솔베이트(polysorbate), 비타민 E TPGS(d-α-tocopheryl polyethylene glycol succinate; BASF), 겔루시레 50/13(Gelucire 50/13; Gattefosse), Kolliphor HS 15(BASF), PEG6000(SAMCHUN), 콜리돈 30(Kollidon 30; BASF) 등을 사용할 수 있다.In addition, as a suitable auxiliary solubilizer, soluplus, polysorbate, vitamin E TPGS (d-α-tocopheryl polyethylene glycol succinate; BASF), Gelucire 50/13 (Gelucire 50/13; Gattefosse) ), Kolliphor HS 15 (BASF), PEG6000 (SAMCHUN), Kollidon 30 (BASF), and the like can be used.
하기 표 2는 본 발명의 일 실시예에 사용된 필름 형성제인 폴리에틸렌옥사이드 및 가용화제인 폴록사머 188의 물리화학적 특성을 나타낸 것이다.Table 2 below shows the physical and chemical properties of polyethylene oxide as a film forming agent and poloxamer 188 as a solubilizing agent used in one embodiment of the present invention.
상기 산도조절제(acidity regulator)는 상기 필름의 pH를 적정한 범위로 조절하여 약물을 용해도를 높일 수 있는 제제로, 시트릭산(citric acid), 아세트산(acetic acid), 락트산(lactic acid), 타르타르산(tartaric acid), 프마르산(fumaric acid) 등의 유기산 제제가 선택될 수 있고, 바람직하게는 시트릭산일 수 있으나, 이에 제한되는 것은 아니다.The acidity regulator is an agent capable of increasing drug solubility by adjusting the pH of the film to an appropriate range, and includes citric acid, acetic acid, lactic acid, and tartaric acid. acid, fumaric acid, etc. may be selected, preferably citric acid, but is not limited thereto.
상기 시트릭산은 상기 필름 전체 100 중량부에 대하여, 1 내지 2 중량부, 바람직하게는 1.1 내지 1.3 중량부, 보다 바람직하게는 1.2 중량부로 포함되어, pH 5 내지 7, 바람직하게는 pH 5.24 내지 6.41을 가지는 구강붕해필름을 만들 수 있다.The citric acid is included in an amount of 1 to 2 parts by weight, preferably 1.1 to 1.3 parts by weight, more preferably 1.2 parts by weight, based on 100 parts by weight of the total film, and has a pH of 5 to 7, preferably pH 5.24 to 6.41. It is possible to make an orally disintegrating film having
상기 산도조절제의 함량이 상기 범위를 초과하면 구강붕해필름의 산도가 구강 내를 손상시킬 수 있는 범위로 낮아질 수 있으며, 상기 범위 미만으로 함유할 경우 구강붕해필름이 염기에 가까워져 아리피프라졸의 용출률에 영향을 미칠 수 있기에, 상기 범위가 바람직하다.If the content of the acidity regulator exceeds the above range, the acidity of the oral dispersible film may be lowered to a range that can damage the oral cavity. Since it can affect, the above range is preferable.
본 발명에 따른 QR 코드가 적용된 구강붕해필름에 있어서, 상기 약물, 폴리에틸렌옥사이드, 폴록사머 및 시트릭산은 1 : 10 : 1 : (0.1~0.2)의 질랑비로 포함될 수 있다. In the oral disintegrating film to which the QR code is applied according to the present invention, the drug, polyethylene oxide, poloxamer, and citric acid may be included in a weight ratio of 1: 10: 1: (0.1 to 0.2).
본 발명의 일 실험예에 따르면, 아리피프라졸 20mg, 폴리에틸렌옥사이드 N10 200mg, 폴록사머 188 20mg, 시트릭산 3mg일 때, 필름의 유연성과 인장강도, 필름의 두께 등의 물리적 성질이 적합하고, 구강붕해속도, 약물 용해도 등도 우수한 것으로 확인되었다.According to an experimental example of the present invention, when 20 mg of aripiprazole, 200 mg of polyethylene oxide N10, 20 mg of
상기 구강붕해필름은 200 내지 230μm의 두께, 바람직하게는 210 내지 220μm의 두께를 가질 수 있다. 일반적으로 150μm에서 250μm 범위의 필름 제제가 환자에게 적합한 바, 본 발명에 따른 구강붕해필름도 환자에게 적합한 범위의 두께를 가질 수 있다.The oral disintegrating film may have a thickness of 200 to 230 μm, preferably 210 to 220 μm. In general, since a film formulation in the range of 150 μm to 250 μm is suitable for patients, the oral disintegrating film according to the present invention may also have a thickness in a range suitable for patients.
상기 구강붕해필름은 4 내지 6 MPa의 우수한 인장강도를 가져 보관 중 파손의 위험을 감소시킬 수 있다.The oral disintegrating film has an excellent tensile strength of 4 to 6 MPa, which can reduce the risk of breakage during storage.
또한, 상기 구강붕해필름은 구강에서 15 내지 25초 이내에 빠르게 붕해될 수 있고, 이에 따라 상기 필름 내 균일하게 함유된 약물이 빠르게 용출되어 효과적으로 전달될 수 있다. In addition, the oral disintegrating film can be rapidly disintegrated in the oral cavity within 15 to 25 seconds, and accordingly, the drug uniformly contained in the film can be rapidly dissolved and effectively delivered.
본 발명에 따른 QR 코드가 적용된 구강붕해필름에 있어서, 상기 구강붕해필름은 QR 코드 리더 기능을 가진 기기로 상기 구강붕해필름 상에 표지된 QR 코드를 인식하여 상기 환자 정보 또는 약물 정보를 확인할 수 있다. In the oral disintegrating film to which the QR code is applied according to the present invention, the oral disintegrating film recognizes the QR code marked on the oral disintegrating film with a device having a QR code reader function to obtain the patient information or drug information. You can check.
또는 QR 코드에 포함된, 상기 환자 정보 또는 약물 정보가 개시된 인터넷상 파일 주소(URL)를 인식하여 인터넷 페이지로 접속함으로써, 상기 환자 정보 또는 약물 정보를 확인할 수 있다.Alternatively, the patient information or drug information may be checked by recognizing a file address (URL) included in the QR code on the Internet where the patient information or drug information is disclosed and accessing the Internet page.
상기 QR 코드 리더 기능을 가진 기기는 상기의 기능을 가진 스마트폰, 카메라, QR 코드 리더기, QR 코드 스캐너 등을 포함할 수 있으나, 이에 제한되는 것은 아니다.The device having the QR code reader function may include, but is not limited to, a smartphone, a camera, a QR code reader, a QR code scanner, and the like having the above function.
상기 환자 정보 또는 약물 정보는 환자의 연령, 성별, 건강상태, 질환의 종류, 중증도, 처방 약물 종류, 약물에 대한 민감도, 복용량, 복용시간, 복용기간, 및 복용방법으로 이루어진 군에서 선택될 수 있으나, 이에 제한되는 것은 아니다.The patient information or drug information may be selected from the group consisting of the patient's age, gender, health condition, type of disease, severity, type of prescription drug, sensitivity to drug, dosage, administration time, administration period, and administration method. , but is not limited thereto.
본 발명은 항정신제 약물, 필름 형성제, 가용화제, 및 산도조절제를 혼합하여 혼합물을 제조하는 단계; 및 상기 제조된 혼합물을 3D 프린터 압출기에 로딩하고 용융·압출시켜 구강붕해필름을 형성하며, 이와 동시에 환자 정보, 약물 정보 또는 상기 정보가 포함된 인터넷상 파일 주소(URL)를 포함하는 QR 코드를 상기 구강붕해필름 상에 생성하는 단계;를 포함하는 QR 코드가 적용된 구강붕해필름 제조방법을 제공한다.The present invention comprises preparing a mixture by mixing an antipsychotic drug, a film former, a solubilizer, and an acidity regulator; And the prepared mixture is loaded into a 3D printer extruder and melted and extruded to form an oral disintegrating film, and at the same time, a QR code including patient information, drug information, or a file address (URL) on the Internet containing the information It provides an oral disintegrating film manufacturing method to which a QR code is applied, including the step of generating on the oral disintegrating film.
상기 약물, 필름 형성제, 가용화제, 및 산도조절제는 3D 프린팅을 할 때에 원활하게 인쇄가 될 수 있는 제제로 선택될 수 있다. The drug, film forming agent, solubilizer, and acidity regulator may be selected as an agent that can be printed smoothly during 3D printing.
상기 혼합물을 제조하는 단계는, 아리피프라졸(aripiprazole) 또는 팔리페리돈(paliperidone)에서 선택되는 항정신제 약물, 필름 형성제로서 폴리에틸렌옥사이드, 가용화제로서 폴록사머, 및 산도조절제로서 시트릭산을 혼합함으로써 수행될 수 있다.The step of preparing the mixture is carried out by mixing an antipsychotic drug selected from aripiprazole or paliperidone, polyethylene oxide as a film former, poloxamer as a solubilizer, and citric acid as an acidity regulator. can
상기 폴록사머는 상기 폴리에틸렌옥사이드 100 중량부에 대하여, 10 중량부로 혼합될 수 있고, 상기 시트릭산은 상기 혼합물 전체 100 중량부에 대하여, 1 내지 2 중량부, 바람직하게는 1.1 내지 1.3 중량부, 보다 바람직하게는 1.2 중량부로 혼합되어 상기 구강붕해필름이 pH 5 내지 7, 바람직하게는 pH 5.24 내지 6.41로 제조될 수 있다.The poloxamer may be mixed in 10 parts by weight based on 100 parts by weight of the polyethylene oxide, and the citric acid may be mixed in an amount of 1 to 2 parts by weight, preferably 1.1 to 1.3 parts by weight, based on 100 parts by weight of the total mixture. Preferably, it is mixed in 1.2 parts by weight so that the oral disintegrating film may be prepared at
바람직하게는, 상기 약물, 폴리에틸렌옥사이드, 폴록사머 및 시트릭산은 1 : 10 : 1 : (0.1~0.2)의 질랑비로 혼합될 수 있다.Preferably, the drug, polyethylene oxide, poloxamer, and citric acid may be mixed in a mixing ratio of 1:10:1: (0.1 to 0.2).
이에 상응하는 특징들은 상술된 부분에서 대신할 수 있다.Corresponding features may be substituted in the foregoing.
상기 구강붕해필름을 형성하는 단계는, 상기 제조된 혼합물을 3D 프린터 압출기에 로딩하고 용융·압출 등 적절한 제조공정을 통해 수행될 수 있다.Forming the oral disintegrating film may be performed by loading the prepared mixture into a 3D printer extruder and performing an appropriate manufacturing process such as melting and extruding.
상기 구강붕해필름은 290 내지 360kPa, 바람직하게는 300 내지 350kPa 공압; 및 110 내지 150℃, 바람직하게는 120 내지 140℃, 보다 바람직하게는 140℃의 압출온도;에서 핫멜트공압(hot melt pneumatic, HMP) 방식의 3D 프린터로 제조될 수 있다. The oral disintegrating film is 290 to 360 kPa, preferably 300 to 350 kPa air pressure; And 110 to 150 ℃, preferably 120 to 140 ℃, more preferably extrusion temperature of 140 ℃; it can be manufactured with a hot melt pneumatic (hot melt pneumatic, HMP)
본 발명의 일 실시예에 따르면, 필라멘트 형태의 열가소성 물질을 노즐안에서 녹여 프린팅을 하는 FDM 방식이 아닌, 필라멘트를 사용하지 않고 직접 파우더를 사용하여 압출하는 방식을 사용하였다.According to one embodiment of the present invention, a method of extruding using powder directly without using a filament was used instead of the FDM method of printing by melting a thermoplastic material in the form of a filament in a nozzle.
상기 조건에서의 3D 프린팅 속도는 2 내지 5mm/s이며, 노즐의 크기는 0.2 내지 0.4mm일 수 있으며, Fusion 360 소프트웨어를 사용하여 디자인될 수 있다.The 3D printing speed under the above conditions is 2 to 5 mm/s, the size of the nozzle may be 0.2 to 0.4 mm, and it may be designed using Fusion 360 software.
상기 구강붕해필름 형성과 동시에, 환자 정보, 약물 정보 또는 상기 정보가 포함된 인터넷상 파일 주소(URL)를 포함하는 QR 코드를 상기 구강붕해필름 상에 생성하는 단계가 수행될 수 있다.Simultaneously with the formation of the oral disintegrating film, a step of generating a QR code including patient information, drug information, or a file address (URL) on the Internet including the information on the oral disintegrating film may be performed.
상기 구강붕해필름 상에 생성된 QR 코드는 스마트폰 등의 QR 코드 리더 기능을 통해 환자 정보, 약물 정보 등을 쉽게 파악할 수 있고, 환자의 복약순응도와 신뢰도를 증가시킬 수 있으며, 의사, 약사, 환자 간에 있어서 상호 커뮤니케이션이 가능할 수 있다.The QR code generated on the oral disintegrating film can easily grasp patient information, drug information, etc. through the QR code reader function of a smartphone, etc., can increase the patient's medication compliance and reliability, and can be used by doctors, pharmacists, Mutual communication between patients may be possible.
상기 구강붕해필름은 약학적으로 허용가능한 적절한 담체와 배합될 수 있고, 필요에 따라, 부형제, 희석제, 분산제, 유화제, 완충제, 안정제, 결합제, 붕해제, 용제 등을 더 포함하여 제조될 수 있다. The oral dispersible film may be formulated with an appropriate pharmaceutically acceptable carrier and, if necessary, may further contain excipients, diluents, dispersants, emulsifiers, buffers, stabilizers, binders, disintegrants, solvents, and the like. .
또한, 본 발명은 상기 제조방법에 따라 제조된 QR 코드가 적용된 구강붕해필름을 제공한다.In addition, the present invention provides an oral disintegrating film to which a QR code is applied manufactured according to the above manufacturing method.
이에 상응하는 특징들은 상술된 부분에서 대신할 수 있다.Corresponding features may be substituted in the foregoing.
이하, 본 발명의 이해를 돕기 위하여 실시예를 들어 상세하게 설명하기로 한다. 다만 하기의 실시예는 본 발명의 내용을 예시하는 것일 뿐 본 발명의 범위가 하기 실시예에 한정되는 것은 아니다. 본 발명의 실시예는 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, examples will be described in detail to aid understanding of the present invention. However, the following examples are merely illustrative of the contents of the present invention, but the scope of the present invention is not limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.
<실험재료 및 방법><Experiment materials and methods>
1. 물질1. Matter
아리피프라졸(Aripiprazole, ARP)과 팔리페리돈(Paliperidone, PAL)은 동화약품 (Suwon, Korea)에서 공급받았다. 팔리페리돈 팔미테이트(Paliperidone Palmitate, PP)는 명인제약 (Suwon, Korea)에서 공급받았다. 폴리에틸렌옥사이드(Poly(ethylene oxide) 100,000, PEO 100,000 Da, POLYOX WSR N10, Singapore), 폴록사머 188(Poloxamer 188, POX, Pluronic® F-68, USA), 및 시트릭산(Citric acid)은 필름 제조에 사용되었다. 본 실험에 사용된 모든 다른 화학물질은 분석용 등급이었다.Aripiprazole (ARP) and Paliperidone (PAL) were supplied by Dong Wha Pharm (Suwon, Korea). Paliperidone Palmitate (PP) was supplied by Myungin Pharmaceutical (Suwon, Korea). Poly(ethylene oxide) 100,000, PEO 100,000 Da, POLYOX WSR N10, Singapore, Poloxamer 188 (POX, Pluronic® F-68, USA), and citric acid are used to make the film. has been used All other chemicals used in this experiment were of analytical grade.
2. 3D 프린터2. 3D printer
QR 코드가 적용된 구강붕해필름(orodispersible film, ODF) (QRODF)의 3D 모델은 Autodesk의 Fusion 360 소프트웨어로 설계되었다. 압출기 속도와 충전량은 NewCreatorK (ROKIT INVIVO Corp. Korea)에 의해 제어되었다. 도면은 직접 공급 노즐 (ROKIT INVIVO Corp. Korea)을 가진 핫멜트공압(hot melt pneumatic, HMP) 3D 프린터와 호환되도록 설계되었고 3D 모델로 변환되었다. 필름은 0.3×0.3×0.03cm이고, 압출 조건은 5mm/s의 노즐 속도, 0.4mm의 노즐 크기, 100%의 충전량, 및 0.1mm의 레이어 높이로 설정되었다.A 3D model of orodispersible film (ODF) (QRODF) with a QR code was designed with Autodesk's Fusion 360 software. The extruder speed and filling amount were controlled by NewCreatorK (ROKIT INVIVO Corp. Korea). The drawing was designed to be compatible with a hot melt pneumatic (HMP) 3D printer with a direct feed nozzle (ROKIT INVIVO Corp. Korea) and converted to a 3D model. The film was 0.3 x 0.3 x 0.03 cm, and the extrusion conditions were set to a nozzle speed of 5 mm/s, a nozzle size of 0.4 mm, a filling amount of 100%, and a layer height of 0.1 mm.
도 1은 본 발명의 일 실시예에 따른 QR 코드가 적용된 구강붕해필름(QRODF)의 제조 방법 및 이의 활용 형태를 개략적으로 나타낸 것이다.1 schematically shows a method of manufacturing an oral disintegrating film (QRODF) to which a QR code is applied and a form of use thereof according to an embodiment of the present invention.
<실험예 1> 3D 프린터를 이용한 제조의 최적화 조건 설정<Experimental Example 1> Setting Optimization Conditions for Manufacturing Using a 3D Printer
3D 프린터의 제조 조건을 최적화하기 위하여, 아리피프라졸(ARP) 및 다른 성분을 첨가하지 않은 폴리에틸렌옥사이드(PEO) (200mg base)의 필름 형성 기능을 하기 표 3에 따른 기압과 압출 온도(extrusion temperature)에 따라 예비 실험을 진행하였다.In order to optimize the manufacturing conditions of the 3D printer, the film formation function of polyethylene oxide (PEO) (200mg base) without adding aripiprazole (ARP) and other components was adjusted according to the air pressure and extrusion temperature according to Table 3 below. A preliminary experiment was conducted.
실험은 100℃에서 시작하여 30분마다 20℃씩 온도를 상승시켜 진행하였다. 공압(pneumatic)은 각 온도(100, 120, 140, 및 160℃)에 대해 250kPa에서 시작하여 50kPa 단계 증가(250, 300, 및 350 kPa)로 제어되었다. 압출기에 로딩된 각 혼합물의 최종 중량은 약 5g이었다. The experiment started at 100 °C and proceeded by increasing the temperature by 20 °C every 30 minutes. The pneumatic was controlled in 50 kPa step increments (250, 300, and 350 kPa) starting at 250 kPa for each temperature (100, 120, 140, and 160 °C). The final weight of each mixture loaded into the extruder was about 5 g.
HMP 3D 프린팅 기술의 경우, 습윤성(wettability), 유동성(flowability), 점성(viscosity), 및 페이스트(paste) 특성이 가장 중요한 조건이다. 본 실험예에 사용된 HMP 3D 프린터는 공압 디스펜서의 끝에 강철 팁을 사용하여 폴리머 베이스 잉크를 노즐의 끝 작은 오리피스(orifice)를 통해 보냈다.In the case of
PEO는 이의 유리한 녹는점(65-67℃) 및 핫멜트 압출능력으로 인해 필름 형성제로 선택되었다. 게다가, PEO는 불수용성 약물의 용해 증진을 위한 가용화제로 고려되었다. 제제의 특성은 ODF 제조를 위해 상업적으로 이용 가능한 3D 프린터의 이용이 허용되는 것이어야 한다. PEO was chosen as the film former because of its advantageous melting point (65-67° C.) and hot melt extrudability. In addition, PEO has been considered as a solubilizing agent for enhancing the dissolution of water-insoluble drugs. The properties of the formulation should allow the use of commercially available 3D printers for ODF manufacturing.
압출 여부를 확인하기 위하여 3D 프린터 온도는 20℃ 간격으로 올렸고, 압력은 250kPa에서 350kPa로 올려 차단하였다. 온도가 낮으면 압출이 발생하지 않고, 온도가 너무 높으면 폴리머가 타버릴 수 있어, 최적 온도와 압력은 각각 140℃ 및 350kP로 확인되었다.In order to check the extrusion, the temperature of the 3D printer was raised at 20 ° C intervals, and the pressure was raised from 250 kPa to 350 kPa to block it. If the temperature is low, extrusion does not occur, and if the temperature is too high, the polymer may burn out, so the optimum temperature and pressure were confirmed to be 140 °C and 350 kP, respectively.
PEO 단독으로 적용될 때 필름이 덜 유연했고, 이에 POX는 필름의 유연성을 조절하기 위한 가소재로 사용되었다. The film was less flexible when applied with PEO alone, so POX was used as a plasticizer to control the flexibility of the film.
<실시예 1~10> 3D 프린터를 이용한 구강붕해필름의 제조 <Examples 1 to 10> Preparation of oral disintegrating film using 3D printer
의약 활성성분인 아리피프라졸을 사용하여 하기 표 4와 같은 조성비율로 식별 가능한 QRODF로 형성된, 가로 30mm, 세로 30mm, 두께 3mm의 필름을 프린팅하였다. 각 물질을 블렌더에 넣고 조성물 및/또는 비율을 사용하여 혼합한 뒤, 특정 비율로 혼합된 분말을 HMP 3D 프린터(ROKIT INVIVO Corp. Korea)의 압출기에 로딩하여 필름을 제조하였다. A film having a width of 30 mm, a length of 30 mm, and a thickness of 3 mm formed of a QRODF that can be identified by the composition ratio shown in Table 4 below was printed using aripiprazole, a pharmaceutically active ingredient. After each material was put into a blender and mixed using a composition and/or ratio, the powder mixed in a specific ratio was loaded into an extruder of an
하기 표 4의 수치의 단위는 mg 이다. 하기 실시예에서 활성약물이 포함되지 않은 것은 제제의 처방 확립을 위한 과정이다. 아래 활성약물이 포함되지 아니하는 실시예 중 인장강도와 프린팅 정도를 평가한 뒤, 활성약물과 시트릭산을 포함하여 최적 제제의 타액 산성도를 조정하였다.The unit of the values in Table 4 below is mg. In the following examples, the fact that the active drug is not included is a process for establishing a formulation of the formulation. After evaluating the tensile strength and printing degree among the examples without the active drug below, the saliva acidity of the optimal formulation was adjusted by including the active drug and citric acid.
1
(ODF-1/F1)Example
One
(ODF-1/F1)
2
(ODF-2/F2)Example
2
(ODF-2/F2)
3
(ODF-3/F3)Example
3
(ODF-3/F3)
4
(ODF-4/F4)Example
4
(ODF-4/F4)
5
(ODF-5/F5)Example
5
(ODF-5/F5)
6
(QR-ODF-6
/F3-1)Example
6
(QR-ODF-6
/F3-1)
7
(QR-ODF-7
/F3-2)Example
7
(QR-ODF-7
/F3-2)
8
(QR-ODF-8
/F3-3)Example
8
(QR-ODF-8
/F3-3)
9
(QR-ODF-9
/F3-4)Example
9
(QR-ODF-9
/F3-4)
10
(QR-ODF-10
/F3-5)Example
10
(QR-ODF-10
/F3-5)
(aripiprazole, APR)Aripiprazole
(aripiprazole, APR)
-
-
-
-
-
-
-
-
-
-
20
20
20
20
20
20
20
20
20
20
옥사이드 N10
(polyethylene
oxide N10, PEO)polyethylene
oxide N10
(polyethylene
oxide N10, PEO)
200
200
200
200
200
200
200
200
200
200
200
200
200
200
200
200
200
200
200
200
(poloxamer 188)Poloxamer 188 (POX)
(poloxamer 188)
-
-
10
10
20
20
30
30
40
40
20
20
20
20
20
20
20
20
20
20
(citric acid)citric acid
(citric acid)
상기 실시예에 따라 제조된 필름에 대해서 하기와 같은 실험을 실시하였다. QR코드를 적용하는데 있어서 가장 핵심적인 요소인 필름의 인장강도와 표면 상태를 보고 결정하였다.The following experiments were conducted on the films prepared according to the above examples. It was determined by looking at the tensile strength and surface condition of the film, which are the most important factors in applying the QR code.
<실험예 2> 필름의 형태학적 분석<Experimental Example 2> Morphological analysis of film
상기 실시예에 따라 제조된 필름의 표면 형태는 5kV에서 전계방사형 주사전자현미경 (FE-SEM, JEOL, JSM-7900F, Tokyo, Japan)에 의해 측정되었다. 필름은 10분 동안 얇은 백금층으로 미리 코팅되었다.The surface morphology of the film prepared according to the above example was measured by a field emission scanning electron microscope (FE-SEM, JEOL, JSM-7900F, Tokyo, Japan) at 5 kV. The film was pre-coated with a thin layer of platinum for 10 minutes.
도 2는 본 발명의 일 실험예에 따른 필름 표면의 주사전자현미경 이미지로, 이를 참조하면, PEO 만으로 제조된 실시예 1(F1)의 표면이 거친 것으로 관찰되었고, 실시예 2(F2), 실시예 4(F4) 및 실시예 5(F5) 제형에서는 폴록사머(POX)를 포함하더라도 필름이 불균일한 것으로 관찰되었다.2 is a scanning electron microscope image of the surface of a film according to an experimental example of the present invention. Referring to this, it was observed that the surface of Example 1 (F1) made of only PEO was rough, and Example 2 (F2), In the formulations of Example 4 (F4) and Example 5 (F5), it was observed that the film was non-uniform even though poloxamer (POX) was included.
반면, PEO/POX의 비가 10:1인 실시예 3(F3)의 표면은 다른 제형에서 확인할 수 없는, 깨끗한 프린팅 라인을 가지는 매끄러운 표면을 나타내었다. 따라서, POX가 PEO 기반의 ODF의 유연성을 조절하는 데 중요한 역할을 함을 확인할 수 있다. On the other hand, the surface of Example 3 (F3) having a PEO/POX ratio of 10:1 showed a smooth surface with clear printing lines, which could not be confirmed in other formulations. Therefore, it can be confirmed that POX plays an important role in controlling the flexibility of PEO-based ODF.
<실험예 3> 필름의 인장강도 분석<Experimental Example 3> Analysis of tensile strength of film
500 N-로드 셀을 갖는 H5KT 텍스처 분석기 (Tinius Olsen Corp)를 사용하여 QRODF의 유연성을 확인하기 위해 인장강도를 측정하였다. 인장강도가 높은 필름은 보관 중 파손의 염려가 적다.Tensile strength was measured to confirm the flexibility of the QRODF using an H5KT texture analyzer (Tinius Olsen Corp) with a 500 N-load cell. Films with high tensile strength are less likely to break during storage.
필름은 5×5mm 크기로 미리 절단하고, 각각의 측정에 대해, 스트립을 25℃에서 밸런싱하고 텍스처 분석기의 텐션 그립에 수직으로 놓았다. 크로스 헤드 속도는 0.04inch/min으로 제어되었다. 필름이 파손된 후 시험을 중단하고, 단점의 최대 하중을 기록하였다. The film was pre-cut to a size of 5x5 mm, and for each measurement, the strip was balanced at 25° C. and placed vertically in the tension grips of the texture analyzer. The crosshead speed was controlled at 0.04 inch/min. The test was stopped after the film broke and the maximum load at the point was recorded.
도 3 및 하기 표 5는 본 발명의 일 실험예에 따른 필름의 인장강도를 측정한 결과로, 이를 참조하면, 활성약물이 포함되지 않은 실시예 1(ODF-1) 내지 실시예 5(ODF-5) 중에서는 상기 실시예 1(ODF-1), 실시예 2(ODF-2) 및 실시예 3(ODF-3)에 따라 제조된 필름에서 가장 높은 인장강도를 나타냈다. 실시예 4(ODF-4) 및 실시예 5(ODF-5)에 따라 제조된 필름은 깨지기 쉬운 상태의 인장강도를 나타냈다. Figure 3 and Table 5 below show the results of measuring the tensile strength of films according to one experimental example of the present invention. Referring to these, examples 1 (ODF-1) to 5 (ODF- 5), the films prepared according to Example 1 (ODF-1), Example 2 (ODF-2) and Example 3 (ODF-3) showed the highest tensile strength. The films prepared according to Example 4 (ODF-4) and Example 5 (ODF-5) exhibited tensile strength in the brittle state.
상세하게는, 실시예 3의 인장강도는 5±0.8MPa였고, 실시예 4는 1.91±1.22MPa로 가장 낮은 인장강도를 나타냈다. 실시예 3을 기초로 시트릭산을 첨가한 필름(QR-ODF-6 내지 QR-ODF-10)은 실시예 3과 유사한 강도를 나타냈다.Specifically, the tensile strength of Example 3 was 5 ± 0.8 MPa, Example 4 showed the lowest tensile strength of 1.91 ± 1.22 MPa. Films to which citric acid was added based on Example 3 (QR-ODF-6 to QR-ODF-10) exhibited strength similar to Example 3.
또한, 첨가되는 POX의 양에 따라 강도가 변하는 것으로 나타났다. POX가 PEO의 10중량%를 초과하면 취약한 제제가 되었다. In addition, the strength was found to change depending on the amount of POX added. POX greater than 10% by weight of PEO resulted in brittle formulations.
상기 내용에 따라서 실시예 3이 QR코드가 적용된 구강붕해필름에 사용하기 적합한 제제로 판단되어, 하기 내용부터 실시예 3(ODF-3)의 처방을 기반으로 한 실험을 진행하였다.According to the above, Example 3 was determined to be a formulation suitable for use in the oral disintegrating film to which the QR code was applied, and an experiment based on the prescription of Example 3 (ODF-3) was conducted from the following information.
<실험예 4> 필름 두께 분석<Experimental Example 4> Film thickness analysis
필름의 두께는 정압 두께 측정 장치 PG-12J (TECLOCK Co., Ltd., Nagoya, Japan)로 측정되었다 (n=3).The thickness of the film was measured with a constant pressure thickness measuring device PG-12J (TECLOCK Co., Ltd., Nagoya, Japan) (n = 3).
일반적으로 150μm에서 250μm 범위의 필름 제제가 환자에게 적합하다. 본 실험예를 통해 분석한 결과, 하기 표 6과 같이, 상기 실시예에 따라 프린트된 필름은 158μm 내지 366μm의 범위의 두께를 가지며, 최종적으로는 219μm로, 환자에게 적합한 두께임을 확인할 수 있었다.Generally, film formulations in the range of 150 μm to 250 μm are suitable for patients. As a result of analysis through this experimental example, as shown in Table 6 below, it was confirmed that the printed film according to the above embodiment had a thickness in the range of 158 μm to 366 μm, and finally 219 μm, which was a suitable thickness for the patient.
한편, POX의 농도가 증가함에 따라 필름의 두께가 증가되는 것으로 나타났다. POX는 예비 프린팅(pre-printing) 혼합물의 녹는점에 영향을 미칠 수 있으므로, 가열된 혼합물의 유동성을 다른 농도의 POX로 조절할 수 있다. 폴리머 혼합물의 더 높은 유동성은 더 높은 인쇄 질량을 전달할 수 있고, 그 두께는 POX의 다양한 농도에 의해 영향을 받았다.On the other hand, it was found that the thickness of the film increased as the concentration of POX increased. Since POX can affect the melting point of the pre-printing mixture, the flowability of the heated mixture can be adjusted with different concentrations of POX. The higher flowability of the polymer mixture can deliver higher print mass, and its thickness was affected by varying concentrations of POX.
<실험예 5> 필름의 pH 분석<Experimental Example 5> pH analysis of film
구강의 자극을 피하고 필름으로부터 약물 용해를 향상시키기 위해 필름 표면의 pH를 조정하였다.The pH of the film surface was adjusted to avoid irritation of the oral cavity and improve drug dissolution from the film.
상기 실시예 6 내지 10을 취해 포스페이트 버퍼(pH 6.8) 5 mL에 용해시킨 후, pH 미터기 (A211, Thermo Scientific, USA)를 이용하여 pH를 측정하였다. 측정 전, pH 미터기는 일련의 기준 표준 (pH 4, 7, 및 10 standard solutions, Sigma)으로 보정되었다. 각 시료의 측정은 3회씩 수행되었다.After dissolving the above Examples 6 to 10 in 5 mL of phosphate buffer (pH 6.8), the pH was measured using a pH meter (A211, Thermo Scientific, USA). Before measurement, the pH meter was calibrated with a series of reference standards (
그 결과, 하기 표 7과 같이, 시트릭산의 첨가에 비례하여 필름의 pH가 감소하는 것으로 나타났다. 시트릭산이 첨가되지 않은 필름의 pH는 8.79 내지 8.14에서 측정되었고 시트릭산이 첨가된 필름의 pH는 5.24 내지 6.41을 나타냈다. 이는 pH 범위가 목표 pH 내에 있고 구강에 적합함을 의미한다.As a result, as shown in Table 7 below, it was found that the pH of the film decreased in proportion to the addition of citric acid. The pH of the film without citric acid was measured at 8.79 to 8.14, and the pH of the film with citric acid was 5.24 to 6.41. This means that the pH range is within the target pH and suitable for oral use.
<실험예 6> 필름의 붕해 시간 분석<Experimental Example 6> Analysis of disintegration time of film
붕해(disintegration) 실험은 37±0.5℃에서 DIT-200 붕해 장치 (Labfine Inc., Korea)로 수행되었다. 각 용기는 붕해 매질로서 900mL의 정제수를 함유하였다. 붕해 시간은 필름이 붕괴되어 메쉬를 통과할 때 측정되었다. 모든 측정은 각각의 제형에 대해 3회씩 수행되었다.Disintegration experiments were performed with a DIT-200 disintegration apparatus (Labfine Inc., Korea) at 37±0.5°C. Each vessel contained 900 mL of purified water as disintegration medium. Disintegration time was measured when the film collapsed and passed through the mesh. All measurements were performed in triplicate for each formulation.
빠른 분해는 필름 제형에서 중요한 품질 속성으로, 약전(pharmacopoeia)에는 ODF 붕해 시간에 대한 기준이 없는 바, ODF 붕해 시간에 대한 표준 요건이 고려되었다. CDER 지침에 따르면, 경구 붕해 정제의 붕해 시간은 30초를 넘지 않아야 한다.Rapid disintegration is an important quality attribute in film formulations, and since there is no standard for ODF disintegration time in pharmacopoeia, standard requirements for ODF disintegration time have been considered. According to CDER guidelines, the disintegration time of an orally disintegrating tablet should not exceed 30 seconds.
본 실험예에 따라 붕해 시간을 분석한 결과, 하기 표 8과 같이, 상기 실시예에 따라 제조된 필름에 대한 붕해 시간이 19.7초 내지 22.2초 범위로 나타났다. 필름 제형은 정제보다 다공성이 높기 때문에 붕해 시간이 더 단축될 수 있다. 따라서, 상기 실시예에 따라 제조된 필름은 구강 내에서 빠르게 붕해될 수 있다.As a result of analyzing the disintegration time according to this experimental example, as shown in Table 8 below, the disintegration time for the film prepared according to the above example was found to be in the range of 19.7 seconds to 22.2 seconds. Film formulations are more porous than tablets, so the disintegration time may be shorter. Therefore, the film prepared according to the above embodiment can rapidly disintegrate in the oral cavity.
<실험예 7> 필름의 약물 함량 균일성 분석<Experimental Example 7> Analysis of drug content uniformity of film
아리피프라졸의 함량 균일성 평가는 3×10cm의 약물 로딩된 QRODF를 90% ACN에 용해시킨 후, 10분 동안 초음파 처리하여 필름으로부터 약물을 추출하였다. To evaluate the uniformity of the content of aripiprazole, a drug-loaded QRODF of 3 × 10 cm was dissolved in 90% ACN, and the drug was extracted from the film by ultrasonic treatment for 10 minutes.
이어서, 필터(0.45μm)를 이용하여 각 시료를 여과시킨 후, 고성능 액체 크로마토그래피(HPLC, Waters Corp., Massachusetts, USA)를 이용하여 약물 함량, 표준편차, 상대표준편차를 분석하였다. 보정 곡선은 0.0625 내지 1mg/mL (R2> 0.999)의 범위였다.Then, after each sample was filtered using a filter (0.45 μm), drug content, standard deviation, and relative standard deviation were analyzed using high-performance liquid chromatography (HPLC, Waters Corp., Massachusetts, USA). The calibration curve ranged from 0.0625 to 1 mg/mL (R 2 >0.999).
그 결과, 하기 표 9와 같이, 약물이 함유된 모든 제제의 약물 함량은 96.42% 내지 104.89%의 범위로 나타났다. 모든 경우에, 투여 단위의 균일성은 설정된 한계 (L1±15%) 내에 있었다.As a result, as shown in Table 9 below, the drug content of all drug-containing formulations ranged from 96.42% to 104.89%. In all cases, the uniformity of dosage units was within established limits (L1±15%).
<실험예 8> 필름의 시차 주사 열량 (DSC) 분석<Experimental Example 8> Differential Scanning Calorimetry (DSC) Analysis of Film
본 실험에 사용된 PEO 및 POX의 압출된 QRODF의 물리적 상태를 결정하기 위해 시차 주사 열량 분석(DSC)을 수행하였다. DSC를 통해 가공 방법이 제제, 물질 및 순수한 약물의 결정도에 미치는 영향을 확인할 수 있다. 시차 주사 열량계(Differential Scanning Calorimetry; DSC, 200, F3 Maia, NETZSCH, Germany)를 사용하여 ARP, PEO, POX, 시트릭산 및 QRODF의 열역학적 특성을 분석하였다. 모든 측정은 5℃ 내지 250℃에서 10℃/min의 스캐닝 속도로 수행되었다.Differential scanning calorimetry (DSC) was performed to determine the physical state of the extruded QRODFs of PEO and POX used in this experiment. DSC allows the determination of the effect of processing methods on the crystallinity of formulations, substances and pure drugs. The thermodynamic properties of ARP, PEO, POX, citric acid and QRODF were analyzed using differential scanning calorimetry (DSC, 200, F3 Maia, NETZSCH, Germany). All measurements were performed between 5 °C and 250 °C at a scanning rate of 10 °C/min.
도 4는 본 발명의 일 실험예에 따라 수행된 시차 주사 열량 분석 결과로, 이를 참조하면, PEO와 POX는 각각 67.7℃와 54.6℃에서 용융 피크를 나타냈다. POX를 PEO 기반 필름에 첨가함으로써 실시예 9(F3-4)의 흡열 피크가 67.7℃에서 65℃로 이동하여, POX가 프린트된 혼합물의 녹는점 조절에 미치는 영향을 나타내었다. 4 is a differential scanning calorimetry analysis result performed according to an experimental example of the present invention. Referring to this, PEO and POX showed melting peaks at 67.7 ° C and 54.6 ° C, respectively. By adding POX to the PEO-based film, the endothermic peak of Example 9 (F3-4) shifted from 67.7 °C to 65 °C, indicating the effect of POX on the melting point control of the printed mixture.
또한, ARP의 융점 피크는 F3-4의 스펙트럼에서 사라져서, ARP의 결정성이 QRODF에서 완전히 비정질 상태로 변화될 수 있음을 확인할 수 있다.In addition, the melting point peak of ARP disappeared from the spectrum of F3-4, confirming that the crystallinity of ARP can be completely changed to an amorphous state in QRODF.
<실험예 9> 분말형 X-선 회절 (PXRD) 분석<Experimental Example 9> Powder X-ray diffraction (PXRD) analysis
QRODF, PEO, POX, 시트릭산 및 순수한 ARP를 포함한 각 시료의 PXRD 패턴을 40kV 전압 및 150mA 전류에서 Cu-K 방사선을 이용한 분말형 X-선 회절계 (D/max-2500V/PC, Rigaku, Japan)로 분석하였다. 시료는 1s/scan의 속도로 5°에서 60°로 0.02°씩 증가하며 스캔되었다.The PXRD patterns of each sample, including QRODF, PEO, POX, citric acid, and pure ARP, were analyzed using a powder X-ray diffractometer (D/max-2500V/PC, Rigaku, Japan) using Cu-K radiation at a voltage of 40 kV and a current of 150 mA. ) was analyzed. The sample was scanned in increments of 0.02° from 5° to 60° at a speed of 1 s/scan.
도 5는 본 발명의 일 실험예에 따라 수행된 X-선 회절 분석 결과로, 이를 참조하면, 순수한 ARP의 PXRD 패턴은 20.28°, 22.00°, 및 24.78°에서 고 강도의 많은 특징적인 피크를 나타내어, ARP는 본질적으로 결정성이 높음을 나타냈다. 하지만, ARP의 특징적인 피크는 실시예 9(F3-4)의 패턴에서 사라져, ODF에서 약물 결정의 비정질 상태로의 전환을 나타내었다. 이 결과는 DSC 분석 결과를 뒷받침한다.5 is an X-ray diffraction analysis result performed according to an experimental example of the present invention. Referring to this, the PXRD pattern of pure ARP shows many characteristic peaks of high intensity at 20.28 °, 22.00 °, and 24.78 ° , indicated that ARP was highly crystalline in nature. However, the characteristic peak of ARP disappeared from the pattern of Example 9 (F3-4), indicating the conversion of drug crystals in ODF to an amorphous state. This result supports the results of the DSC analysis.
<실험예 10> 필름의 의약 활성성분의 용해도 평가<Experimental Example 10> Evaluation of the solubility of the active pharmaceutical ingredient of the film
아리피프라졸의 용출률을 확인하기 위해, pH 1.2 액 (37℃, 500 mL)에서 미국 약전(USP) II (패들법, 속도 50rpm)에 따라 용출시험기(D-TWELVE, DCM, Seoul, Korea)를 사용하여 1시간 동안 용출시험을 수행하였으며, 3회 반복 수행하였다. 시간대 별로 시료를 채취하고 전 처리한 후, 고성능 액체크로마토그래피로 용출률을 분석하였다. In order to confirm the dissolution rate of aripiprazole, a dissolution tester (D-TWELVE, DCM, Seoul, Korea) was used in accordance with the United States Pharmacopoeia (USP) II (paddle method, speed 50 rpm) in a pH 1.2 solution (37 ° C, 500 mL). A dissolution test was performed for 1 hour and repeated three times. Samples were taken for each time period and pre-treated, and then the dissolution rate was analyzed by high-performance liquid chromatography.
도 6 및 하기 표 10은 본 발명의 일 실험예에 따른 구강붕해필름의 약물 방출 정도를 평가한 결과로, 이를 참조하면, 실시예 6(QR-ODF-6)의 약물 방출은 5분에 40.13%에 도달하고 60분 후에 92.91%에 도달하는 것으로 나타났다. Figure 6 and Table 10 below are the results of evaluating the degree of drug release of the oral dispersible film according to an experimental example of the present invention. It was found to reach 40.13% and reach 92.91% after 60 minutes.
제제로부터 약물 방출의 최대 달성을 얻기 위해, 시트릭산을 사용하여 pH 값을 조절하고 아리피프라졸의 용해 속도를 제어하였다. 그 결과, 제제에 시트릭산의 혼입은 아리피프라졸의 용해 속도를 5분에서 71.14% 내지 85.40%로, 60분에서 94.22% 내지 99.19%로 상당히 증가시킬 수 있었다. 따라서, 시트릭산을 함유하는 구강붕해필름은 아리피프라졸의 동역학적으로 빠른 용출을 하게 함을 확인할 수 있다.To obtain maximum achievement of drug release from the formulation, citric acid was used to adjust the pH value and control the dissolution rate of aripiprazole. As a result, the incorporation of citric acid in the formulation could significantly increase the dissolution rate of aripiprazole from 71.14% to 85.40% at 5 minutes and from 94.22% to 99.19% at 60 minutes. Therefore, it can be confirmed that the oral dispersible film containing citric acid enables a kinetically rapid dissolution of aripiprazole.
(min)hour
(min)
(실시예 6)QR-ODF6
(Example 6)
(실시예 7)QR-ODF7
(Example 7)
(실시예 8)QR-ODF8
(Example 8)
(실시예 9)QR-ODF9
(Example 9)
(실시예 10)QR-ODF10
(Example 10)
<실험예 11> QR코드의 인식평가 <Experimental Example 11> QR code recognition evaluation
도 7은 본 발명의 일 실시예에 따라 제조된 QRODF 이미지로, 이를 참조하면, 필름은 30×30mm이고 22.3×22.3mm의 QR 코드로 설계되었다. 상기 필름은 압출된 폴리머로부터 성공적으로 수득되었고, QR 코드는 상기 필름상에 설계되었다.7 is a QRODF image manufactured according to an embodiment of the present invention. Referring to this, the film is 30 × 30 mm and designed as a 22.3 × 22.3 mm QR code. The film was successfully obtained from an extruded polymer and a QR code was designed on the film.
QR 코드가 적용된 구강붕해필름에 있는 QR 코드를 스마트폰으로 인식하여 인식이 되는지를 확인하였다. 상기 필름의 QR 코드는 스마트폰의 QR 스캐닝 어플리케이션을 사용하여 읽었다. 본 실험예에서 QR Code reader (v. 2.1, NAKAYUBI Corp) 및 카메라 앱 (iPhone X, Apple Co.)이 사용되었다. The QR code on the oral disintegrating film to which the QR code was applied was recognized by a smartphone to confirm whether it was recognized. The QR code of the film was read using a QR scanning application on a smartphone. In this experimental example, a QR Code reader (v. 2.1, NAKAYUBI Corp) and a camera app (iPhone X, Apple Co.) were used.
그 결과, QR 코드가 적용된 구강붕해필름에 있는 QR코드는 정상적으로 인식이 되어 스마트폰에 정보가 표기되는 것을 확인할 수 있었다. 이는 QR 코드가 구강붕해필름에 정확하게 적용이 되었다는 것을 의미한다. As a result, it was confirmed that the QR code on the oral disintegrating film to which the QR code was applied was normally recognized and the information displayed on the smartphone. This means that the QR code was accurately applied to the oral disintegrating film.
<실시예 11> 팔리페리돈을 포함하는 구강붕해필름 제조 및 분석<Example 11> Manufacturing and Analysis of Oral Disintegrating Film Containing Paliperidone
상기 실험예는 실시예 3을 기반으로 한 처방이다. 여기에 활성성분만을 달리하여, 아리피프라졸 대신 팔리페리돈(paliperidone) 또는 팔리페리돈 팔미테이트(paliperidone palmitate)를 사용하여 상기 실시예에 따른 방법으로 구강붕해필름을 제조하였다 (도 8, 및 9). 약물 성분에 따라 녹는점이 다르므로, 압출온도는 적절하게 조절되었다. The experimental example is a prescription based on Example 3. Oral disintegrating films were prepared by the method according to the above example, using only the active ingredient, paliperidone or paliperidone palmitate instead of aripiprazole (FIGS. 8 and 9). Since the melting point differs depending on the drug component, the extrusion temperature was appropriately controlled.
실시예 10의 처방에 따라 필름을 제조한 결과, 하기 표 11과 같은 약물방출양상을 나타내었다. (각각 3회 실시)As a result of preparing the film according to the prescription of Example 10, the drug release patterns were shown in Table 11 below. (3 times each)
시간 (min)
time (min)
(팔리페리돈)QR-ODF-PAL
(Paliperidone)
(팔리페리돈 팔미테이트)QR-ODF-PP
(Paliperidone Palmitate)
이상으로 본 발명 내용의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 즉, 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다.Having described specific parts of the present invention in detail above, it is clear to those skilled in the art that these specific descriptions are only preferred embodiments, and the scope of the present invention is not limited thereby. do. That is, the substantial scope of the present invention is defined by the appended claims and their equivalents.
Claims (13)
환자 정보, 약물 정보 또는 상기 정보가 포함된 QR 코드 혹은 환자 정보, 약물 정보 또는 상기 정보가 포함된 인터넷상 파일 주소(URL)를 포함하는 QR 코드가 표지되고,
상기 약물, 폴리에틸렌옥사이드, 폴록사머 및 시트릭산은 1 : 10 : 1 : (0.1~0.2)의 질랑비로 포함되고,
상기 환자 정보 또는 약물 정보는 환자의 연령, 성별, 건강상태, 질환의 종류, 중증도, 처방 약물 종류, 약물에 대한 민감도, 복용량, 복용시간, 복용기간, 및 복용방법으로 이루어진 군에서 선택되고,
상기 폴록사머는 폴록사머 101, 폴록사머 105, 폴록사머 108, 폴록사머 122, 폴록사머 123, 폴록사머 124, 폴록사머 181, 폴록사머 182, 폴록사머 183, 폴록사머 184, 폴록사머 185, 폴록사머 188, 폴록사머 212, 폴록사머 215, 폴록사머 217, 폴록사머 231, 폴록사머 234, 폴록사머 235, 폴록사머 237, 폴록사머 238, 폴록사머 282, 폴록사머 284, 폴록사머 288, 폴록사머 331, 폴록사머 333, 폴록사머 334, 폴록사머 335, 폴록사머 338, 폴록사머 401, 폴록사머 402, 폴록사머 403 또는 폴록사머 407에서 선택되고,
두께가 200 내지 230μm이고, 구강에서 15 내지 25초 이내에 붕해되는 것을 특징으로 하는, QR 코드가 적용된 구강붕해필름.An antipsychotic drug selected from aripiprazole, paliperidone or paliperidone palmitate, polyethylene oxide as a film former, poloxamer as a solubilizer, and citric acid as an acidity regulator,
A QR code including patient information, drug information, or a QR code containing the above information or a QR code including a file address (URL) on the Internet including patient information, drug information, or the above information is displayed,
The drug, polyethylene oxide, poloxamer and citric acid are included in a ratio of 1: 10: 1: (0.1 to 0.2),
The patient information or drug information is selected from the group consisting of the patient's age, gender, health condition, type of disease, severity, type of prescription drug, sensitivity to drug, dosage, administration time, administration period, and administration method,
The poloxamer is poloxamer 101, poloxamer 105, poloxamer 108, poloxamer 122, poloxamer 123, poloxamer 124, poloxamer 181, poloxamer 182, poloxamer 183, poloxamer 184, poloxamer 185, poloxamer 188, poloxamer 212, poloxamer 215, poloxamer 217, poloxamer 231, poloxamer 234, poloxamer 235, poloxamer 237, poloxamer 238, poloxamer 282, poloxamer 284, poloxamer 288, poloxamer 331, It is selected from poloxamer 333, poloxamer 334, poloxamer 335, poloxamer 338, poloxamer 401, poloxamer 402, poloxamer 403 or poloxamer 407;
A thickness of 200 to 230 μm, characterized in that it disintegrates in the oral cavity within 15 to 25 seconds, QR code applied oral disintegrating film.
상기 구강붕해필름은,
4 내지 6 MPa의 인장강도를 가지는 것을 특징으로 하는, QR 코드가 적용된 구강붕해필름.According to claim 1,
The oral disintegrating film,
Characterized in that it has a tensile strength of 4 to 6 MPa, QR code applied orally disintegrating film.
상기 구강붕해필름은,
QR 코드 리더 기능을 가진 기기로 상기 QR 코드를 인식하여 상기 환자 정보 및/또는 약물 정보를 확인할 수 있는 것을 특징으로 하는, QR 코드가 적용된 구강붕해필름.According to claim 1,
The oral disintegrating film,
An oral disintegrating film with a QR code, characterized in that the patient information and / or drug information can be checked by recognizing the QR code with a device having a QR code reader function.
상기 제조된 혼합물을 3D 프린터 압출기에 로딩하고 용융·압출시켜 구강붕해필름을 형성하며, 이와 동시에 환자 정보, 약물 정보 또는 상기 정보가 포함된 QR 코드 혹은 환자 정보, 약물 정보 또는 상기 정보가 포함된 인터넷상 파일 주소(URL)를 포함하는 QR 코드를 상기 구강붕해필름 상에 생성하는 단계;를 포함하는, 제1항에 따른 QR 코드가 적용된 구강붕해필름 제조방법.An antipsychotic drug selected from aripiprazole, paliperidone or paliperidone palmitate, polyethylene oxide as a film former, poloxamer as a solubilizer, and citric acid as an acidity regulator. Preparing; and
The prepared mixture is loaded into a 3D printer extruder, melted and extruded to form an oral disintegrating film, and at the same time, patient information, drug information or a QR code containing the above information or patient information, drug information or the above information is included. Generating a QR code including a file address (URL) on the Internet on the oral disintegrating film; A method for manufacturing an oral disintegrating film to which the QR code according to claim 1 is applied, including.
상기 구강붕해필름은,
290 내지 360kPa 공압 및 110 내지 150℃의 압출온도에서 핫멜트공압(hot melt pneumatic, HMP) 방식의 3D 프린터로 제조되는 것을 특징으로 하는, QR 코드가 적용된 구강붕해필름 제조방법. According to claim 8,
The oral disintegrating film,
290 to 360 kPa pneumatic pressure and extrusion temperature of 110 to 150 ℃, characterized in that produced by a hot melt pneumatic (HMP) method 3D printer, QR code applied oral disintegrating film manufacturing method.
상기 폴록사머는,
상기 폴리에틸렌옥사이드 100 중량부에 대하여, 10 중량부로 혼합되는 것을 특징으로 하는, QR 코드가 적용된 구강붕해필름 제조방법.According to claim 8,
The poloxamer,
An oral disintegrating film manufacturing method with a QR code, characterized in that it is mixed in 10 parts by weight with respect to 100 parts by weight of the polyethylene oxide.
상기 시트릭산은,
상기 혼합물 전체 100 중량부에 대하여, 1 내지 2 중량부로 혼합되어 상기 구강붕해필름이 pH 5 내지 7로 제조되는 것을 특징으로 하는, QR 코드가 적용된 구강붕해필름 제조방법.According to claim 8,
The citric acid is
Based on the total 100 parts by weight of the mixture, it is mixed in 1 to 2 parts by weight, characterized in that the oral disintegrating film is prepared at pH 5 to 7, QR code applied oral disintegrating film manufacturing method.
상기 약물, 폴리에틸렌옥사이드, 폴록사머 및 시트릭산은,
1 : 10 : 1 : (0.1~0.2)의 질랑비로 혼합되는 것을 특징으로 하는, QR 코드가 적용된 구강붕해필름 제조방법.According to claim 8,
The drug, polyethylene oxide, poloxamer and citric acid,
1: 10: 1: (0.1 ~ 0.2) characterized in that the mixing ratio, QR code applied oral disintegrating film manufacturing method.
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