US20030031708A1 - Synergistic filler composition - Google Patents

Synergistic filler composition Download PDF

Info

Publication number
US20030031708A1
US20030031708A1 US09/915,057 US91505701A US2003031708A1 US 20030031708 A1 US20030031708 A1 US 20030031708A1 US 91505701 A US91505701 A US 91505701A US 2003031708 A1 US2003031708 A1 US 2003031708A1
Authority
US
United States
Prior art keywords
tablet
composition
microcrystalline cellulose
copolymer
pvp
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
US09/915,057
Other versions
US6524617B1 (en
Inventor
Antonio Moroni
Nadhamuni Nerella
Gregory Browny
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
ISP Investments LLC
Original Assignee
ISP Investments LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by ISP Investments LLC filed Critical ISP Investments LLC
Assigned to ISP INVESTMENTS INC. reassignment ISP INVESTMENTS INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: NERELLA, NADHAMUNI G., BROWNY, GREGORY DU, MORONI, ANTONIO
Priority to US09/915,057 priority Critical patent/US6524617B1/en
Priority to RU2004105268/15A priority patent/RU2304981C2/en
Priority to CA2454449A priority patent/CA2454449C/en
Priority to MXPA04000666A priority patent/MXPA04000666A/en
Priority to AT02734286T priority patent/ATE327738T1/en
Priority to ES02734286T priority patent/ES2266502T3/en
Priority to EP02734286A priority patent/EP1416918B1/en
Priority to DE60211916T priority patent/DE60211916T2/en
Priority to CNB028185161A priority patent/CN1268320C/en
Priority to BRPI0211439-9A priority patent/BRPI0211439B1/en
Priority to PCT/US2002/014586 priority patent/WO2003011253A1/en
Priority to JP2003516485A priority patent/JP4805537B2/en
Publication of US20030031708A1 publication Critical patent/US20030031708A1/en
Publication of US6524617B1 publication Critical patent/US6524617B1/en
Application granted granted Critical
Assigned to THE BANK OF NOVA SCOTIA, AS ADMINISTRATIVE AGENT reassignment THE BANK OF NOVA SCOTIA, AS ADMINISTRATIVE AGENT SECURITY AGREEMENT Assignors: AQUALON COMPANY, ASHLAND LICENSING AND INTELLECTUAL PROPERTY LLC, HERCULES INCORPORATED, ISP INVESTMENT INC.
Assigned to ISP CAPITAL, INC., VERONA, INC., ISP CHEMICAL PRODUCTS, INC. reassignment ISP CAPITAL, INC. PATENT RELEASE Assignors: JPMORGAN CHASE BANK, N.A. (F/K/A THE CHASE MANHATTAN BANK)
Assigned to ASHLAND LICENSING AND INTELLECTUAL PROPERTY LLC, AQUALON COMPANY, HERCULES INCORPORATED, ISP INVESTMENTS INC. reassignment ASHLAND LICENSING AND INTELLECTUAL PROPERTY LLC RELEASE OF PATENT SECURITY AGREEMENT Assignors: THE BANK OF NOVA SCOTIA
Assigned to ISP INVESTMENTS LLC reassignment ISP INVESTMENTS LLC CONVERSION Assignors: ISP INVESTMENTS INC.
Assigned to THE BANK OF NOVA SCOTIA, AS ADMINISTRATIVE AGENT reassignment THE BANK OF NOVA SCOTIA, AS ADMINISTRATIVE AGENT SECURITY AGREEMENT Assignors: AVOCA, INC., HERCULES LLC, ISP INVESTMENTS LLC, PHARMACHEM LABORATORIES, INC.
Assigned to ISP INVESTMENTS LLC, HERCULES LLC, AVOCA LLC, PHARMACHEM LABORATORIES LLC reassignment ISP INVESTMENTS LLC RELEASE BY SECURED PARTY (SEE DOCUMENT FOR DETAILS). Assignors: THE BANK OF NOVA SCOTIA
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Compositions Of Macromolecular Compounds (AREA)
  • Seeds, Soups, And Other Foods (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

A synergistic filler composition for making pharmaceutical tablets of sufficient tablet hardness at low compression force, and low friability, to preclude damage to the tablet upon further processing, and without requiring a substantial increase in the size of the tablet, comprising (a) a PVP-VA copolymer and (b) a microcrystalline cellulose.

Description

    BACKGROUND OF THE INVENTION
  • 1. Field of the Invention [0001]
  • This invention relates to pharmaceutical tableting, and, more particularly, to a synergistic filler composition which provides increased tablet hardness and low friability at low compression forces without increasing the size of the tablet. [0002]
  • 2. Description of the Prior Art [0003]
  • Many commercial filler materials are used including microcrystalline cellulose and silicified microcrystalline cellulose inn the manufacture of pharmaceutical tablets. Such materials are described in the paper by Tobyn, M. J. in Int. J. of Pharmaceutics, 169, 183-194 (1998). However drugs which are difficult to compress require tableting machines which can operate at high compression forces in order to provide suitable hardness and low friability properties. Also, large amounts of the filler may be necessary to achieve these results, which, disadvantageously, increases the size of the tablet. [0004]
  • Accordingly, it is an object of this invention to provide a drug tableting filler composition of two components which act synergistically with respect to increasing hardness and decreasing friability for pharmaceutical tablets at a given compression force, and without increasing the size of the tablet. [0005]
  • This and other objects and features of the invention will be made apparent from the following description of the invention [0006]
    • IN THE DRAWINGS
  • FIG. 1 is a plot of tablet hardness (KP) vs. concentration (wt. %) of PVP-VA copolymer in a composition with silicified microcrystalline cellulose (silicified MCC/ProSolv®) at a given compression force. [0007]
  • FIG. 2 is a similar plot for mixtures of copolymer and microcrystalline cellulose (MCC [0008] 102).
  • FIG. 3 is a similar plot for a drug tablet of 67 wt. % acetaminophen (APAP) and silicified microcrystalline cellulose, with and without PVP/VA copolymer. [0009]
  • FIG. 4 is a similar plot as FIG. 3 for a composition containing microcrystalline cellulose. [0010]
  • FIG. 5 is a similar plot of 60% aspirin and silicified microcellulose with and without PVP/VA copolymer. [0011]
  • FIG. 6 is a similar plot of a drug tablet with 60 wt. % aspirin and a mix of microcrystalline cellulose (MCC 102) with and without PVP/VA copolymer. [0012]
  • FIG. 7 is a similar plot as FIG. 6 of a drug tablet with 67 wt. % diltiazem HCl as the model drug. [0013]
    • SUMMARY OF THE INVENTION
  • What is described herein is a synergistic filler composition for making pharmaceutical tablets of increased tablet hardness and low friability without substantially increasing the size of the tablet, comprising (a) a PVP-VA copolymer and (b) microcrystalline cellulose. [0014]
  • Preferred compositions are those wherein (b) is a silicified microcrystalline cellulose; and (a) is present in an amount of about 5-30%; most preferably 10-20%. [0015]
  • Other preferred compositions are those wherein (a) comprises, by weight, 80-60% PVP and 20-40% VA. [0016]
    • DETAILED DESCRIPTION OF THE INVENTION
  • In this invention, there is provided synergistic filler compositions of (a) vinyl pyrrolidone-vinyl acetate copolymers, and (b) microcrystalline cellulose, preferably silicified microcrystalline cellulose, which provide a synergistic increase in hardness, and a synergistic decrease in friability, for tableted drugs containing such fillers. These results are achieved herein with only a minimum amount of the filler composition, and without increasing the size of the tablet. [0017]
  • The invention will be further described by reference to the experimental results illustrated in the drawings. [0018]
  • Accordingly, FIGS. 1 and 2 shows a plot of tablet hardness (KP) vs. concentration (wt. %) of PVP-VA copolymer in a composition with microcrystalline cellulose at a given compression force of 2000, 4000 and 6000 lbs. As shown in FIGS. 1 and 2, the composition of the invention provides a synergistic increase in tablet compressibility (hardness) with an increase in the concentration of PVP-VA copolymer in the composition up to about 30 wt. % of PVP/VA copolymer, as evidenced by the convex shape of the curve. The maximum synergistic effect is obtained at about 20 wt. % PVP-VA copolymer. Further increases in copolymer produces only marginal improvement in tablet hardness. [0019]
  • These results contrast with the individual components alone, or PVP-VA copolymer with other known fillers, such as lactose or dicalcium phosphate, where the hardness increase is observed to be only linear with increasing copolymer concentration. [0020]
  • The microcrystalline cellulose component of the composition is available commercially as ProSolv® (silicified microcrystalline cellulose) and as MCC 102 (microcrystalline cellulose). [0021]
  • The advantageous results demonstrated herein for the composition of the invention were obtained similarly for drugs which are difficult to compress into small tablets without using an excessive amount of filler/binder. Such large amounts of filler/binder would preclude formulation of the drug into tablets of high dosage. [0022]
  • Referring now to FIGS. 3 and 4, there is shown the manufacture of drug-containing tablets with the composition of the invention using acetaminophen as a model drug. [0023]
    COMPOSITIONS OF DRUG TABLETS (WT. %)
    FIGS. 3-4
    67 APAP
    30 Copolymer (25 cellulose + 5 PVP/VA)
    2 PVPP (XL)
    0.5 SiO2 (colloid)
    0.5 Mg stearate
    100
    FIGS. 5-6
    60 Aspirin
    37 Copolymer (27 + 10)
    2 PVPP (XL)
    0.5 SiO2
    0.5 Mg stearate
    100
    FIG. 7
    65 Diltiazem HCI
    32 Copolymer (22 + 10)
    2 PVPP (XL)
    0.5 SiO2
    0.5 Mg stearate
    100
  • Similar synergistic effects were obtained for aspirin tablets containing (FIGS. 5 and 6) and for diltiazem HCl (FIG. 7) as model drugs. [0024]
  • In summary, the invention composition herein provides a synergistic action in drug tableting formulations of even difficult to compress drugs. The observed hardness is sufficient to prevent damage to the tablet upon further processing of the tablet, including coating and packaging. The tablet hardness obtained herein is preferably at least 3 KP, and its friability is <0.7%, usually <0.5%. Both properties are indicative of a new and improved composition in the field of drug tableting. [0025]
  • While the invention has been described with particular reference to certain embodiments thereof, it will be understood that changes and modifications may be made which are within the skill of the art. Accordingly, it is intended to be bound only by the following claims, in which: [0026]

Claims (8)

What is claimed is:
1. A synergistic filler composition for making pharmaceutical tablets of sufficient tablet hardness at low compression force, and low friability, to preclude damage to the tablet upon further processing, and without requiring a substantial increase in the size of the tablet, comprising (a) a PVP-VA copolymer and (b) a microcrystalline cellulose.
2. A composition according to claim 1 wherein (a) is present in an amount of about 5-30% by wt. of the composition.
3. A composition according to claim 2 wherein (a) is present in an amount of about 10-20% by wt.
4. A composition according to claim 1 wherein (a) comprises, by weight, 80−60% PVP and 20-40% VA.
5. A composition according to claim 1 wherein (b) is a silicified microcrystalline cellulose.
6. A pharmaceutical tablet including the synergistic filler composition of claim 1 and a drug.
7. A pharmaceutical tablet according to claim 6 wherein said drug is ordinarily a difficult to compress drug.
8. A pharmaceutical tablet according to claim 6 in which said tablet hardness is at least 3 KP, and its friability is <0.7.
US09/915,057 2001-07-25 2001-07-25 Synergistic filler composition Expired - Lifetime US6524617B1 (en)

Priority Applications (12)

Application Number Priority Date Filing Date Title
US09/915,057 US6524617B1 (en) 2001-07-25 2001-07-25 Synergistic filler composition
PCT/US2002/014586 WO2003011253A1 (en) 2001-07-25 2002-05-10 Synergistic filler composition
CA2454449A CA2454449C (en) 2001-07-25 2002-05-10 Synergistic filler composition of pvp-va and silicified mycrocrystalline cellulose for tablet dosage form
MXPA04000666A MXPA04000666A (en) 2001-07-25 2002-05-10 Synergistic filler composition.
AT02734286T ATE327738T1 (en) 2001-07-25 2002-05-10 SYNERGISTIC FILLING COMPOSITION
ES02734286T ES2266502T3 (en) 2001-07-25 2002-05-10 SYNTHETIC FILLING COMPOSITION.
EP02734286A EP1416918B1 (en) 2001-07-25 2002-05-10 Synergistic filler composition
DE60211916T DE60211916T2 (en) 2001-07-25 2002-05-10 SYNERGISTIC FILLING COMPOSITION
CNB028185161A CN1268320C (en) 2001-07-25 2002-05-10 Synergistic filler composition
BRPI0211439-9A BRPI0211439B1 (en) 2001-07-25 2002-05-10 COMPOSITION OF SYNERGISTIC CHARGE AND PHARMACEUTICAL TABLET
RU2004105268/15A RU2304981C2 (en) 2001-07-25 2002-05-10 Synergetic filling agent composition
JP2003516485A JP4805537B2 (en) 2001-07-25 2002-05-10 Synergistic excipient composition

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US09/915,057 US6524617B1 (en) 2001-07-25 2001-07-25 Synergistic filler composition

Publications (2)

Publication Number Publication Date
US20030031708A1 true US20030031708A1 (en) 2003-02-13
US6524617B1 US6524617B1 (en) 2003-02-25

Family

ID=25435143

Family Applications (1)

Application Number Title Priority Date Filing Date
US09/915,057 Expired - Lifetime US6524617B1 (en) 2001-07-25 2001-07-25 Synergistic filler composition

Country Status (12)

Country Link
US (1) US6524617B1 (en)
EP (1) EP1416918B1 (en)
JP (1) JP4805537B2 (en)
CN (1) CN1268320C (en)
AT (1) ATE327738T1 (en)
BR (1) BRPI0211439B1 (en)
CA (1) CA2454449C (en)
DE (1) DE60211916T2 (en)
ES (1) ES2266502T3 (en)
MX (1) MXPA04000666A (en)
RU (1) RU2304981C2 (en)
WO (1) WO2003011253A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070036859A1 (en) * 2005-08-11 2007-02-15 Perry Ronald L Sustained release antihistamine and decongestant composition

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6620900B2 (en) * 2002-02-07 2003-09-16 Isp Investments Inc. Proliferous copolymer of vinyl pyrrolidone and vinyl acetate
JP4776233B2 (en) * 2002-11-12 2011-09-21 エラン ファーマ インターナショナル，リミティド Fast disintegrating solid formulation that is resistant to abrasion and contains pullulan
US7704528B2 (en) * 2003-05-05 2010-04-27 Isp Investments Inc. Binder composition and method for processing poorly compressible drugs into tablets of predetermined hardness and friability
US8168219B2 (en) * 2005-11-30 2012-05-01 Isp Investments Inc. Synergistic binder composition, method for making same, and tablets of an active and said binder having advantageous hardness and friability
ES2738182T3 (en) * 2013-03-12 2020-01-20 Hercules Llc Polypropylene Coated Silica Coated Composition

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU183408B (en) * 1981-04-28 1984-05-28 Chinoin Gyogyszer Es Vegyeszet Process for producing oral ratard pharmaceutical compositions
US5326570A (en) * 1991-07-23 1994-07-05 Pharmavene, Inc. Advanced drug delivery system and method of treating psychiatric, neurological and other disorders with carbamazepine
DE69617245T2 (en) * 1995-08-17 2002-07-25 Csir Pretoria CONTROLLED RELEASE PRODUCTS
AT413647B (en) * 1998-11-26 2006-04-15 Sandoz Ag USE OF A COPOLYMERISATE OF 1-VINYL-2-PYRROLIDONE AND VINYL ACETATE FOR THE PREPARATION OF CEFUROXIMAXETIL-SUBJECTED TABLETS

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070036859A1 (en) * 2005-08-11 2007-02-15 Perry Ronald L Sustained release antihistamine and decongestant composition

Also Published As

Publication number Publication date
BR0211439A (en) 2004-07-20
CA2454449A1 (en) 2003-02-13
CN1556695A (en) 2004-12-22
WO2003011253A1 (en) 2003-02-13
DE60211916T2 (en) 2007-01-04
BRPI0211439B1 (en) 2017-09-19
EP1416918A4 (en) 2004-08-18
DE60211916D1 (en) 2006-07-06
US6524617B1 (en) 2003-02-25
BRPI0211439B8 (en) 2021-05-25
ATE327738T1 (en) 2006-06-15
RU2304981C2 (en) 2007-08-27
MXPA04000666A (en) 2004-04-05
EP1416918B1 (en) 2006-05-31
RU2004105268A (en) 2005-03-10
EP1416918A1 (en) 2004-05-12
CA2454449C (en) 2010-10-26
JP2005501049A (en) 2005-01-13
JP4805537B2 (en) 2011-11-02
ES2266502T3 (en) 2007-03-01
CN1268320C (en) 2006-08-09

Similar Documents

Publication Publication Date Title
EP1274401B2 (en) Stable pharmaceutical compositions containing 7-substituted-3,5-dihydroxyheptanoic acids or 7-substituted-3,5-dihydroxyheptenoic acids
CA2463583A1 (en) Highly compressible ethylcellulose for tableting
JP2009507047A5 (en)
EP1321142A1 (en) Solid pharmaceutical composition for oral administration of Tegaserod
EP0454396A1 (en) Tablet composition and method for problem pharmaceutical materials
EP2983719A1 (en) Manufacturing process for effervescent dosage forms
US6524617B1 (en) Synergistic filler composition
CA2423574A1 (en) Stabilization of solid drug formulations
JP2009513530A5 (en)
AU2002348279C1 (en) Soluble drug extended release system
WO2007016350A2 (en) Modified release tablet formulations with enhanced mechanical properties
US7897172B2 (en) Tablets exhibiting reduced drug release variability
US8168219B2 (en) Synergistic binder composition, method for making same, and tablets of an active and said binder having advantageous hardness and friability
US6737419B2 (en) Benazepril hydrochloride tablet formulations
US20050271718A1 (en) Sustained release propafenone hydrochloride capsules
CA2217238A1 (en) Cross-linked cellulose as a tablet excipient
US20040131672A1 (en) Direct compression pharmaceutical composition containing a pharmaceutically active ingredient with poor flowing properties
WO2008001184A2 (en) Solid composition
WO2002045753A3 (en) Oral extended release formulation of gepirone
AU2005201185B2 (en) Stable pharmaceutical compositions containing 7-substituted-3, 5-dihydroxyheptanoic acids or 7-substituted-3, 5-dihydroxyheptenoic acids
Schwartz et al. Influence of lubricants on the tableting and disintegration time of tablets made up of coprecessed excipients vs. the physical blends
Dressler et al. A Corn Starch/a-Lactose Monohydrate Compound as a Directly Compressible Excipient

Legal Events

Date Code Title Description
AS Assignment

Owner name: ISP INVESTMENTS INC., DELAWARE

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:MORONI, ANTONIO;NERELLA, NADHAMUNI G.;BROWNY, GREGORY DU;REEL/FRAME:012049/0506;SIGNING DATES FROM 20010719 TO 20010723

STCF Information on status: patent grant

Free format text: PATENTED CASE

FEPP Fee payment procedure

Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY

FPAY Fee payment

Year of fee payment: 4

FPAY Fee payment

Year of fee payment: 8

AS Assignment

Owner name: THE BANK OF NOVA SCOTIA, AS ADMINISTRATIVE AGENT,

Free format text: SECURITY AGREEMENT;ASSIGNORS:ASHLAND LICENSING AND INTELLECTUAL PROPERTY LLC;HERCULES INCORPORATED;AQUALON COMPANY;AND OTHERS;REEL/FRAME:026918/0052

Effective date: 20110823

AS Assignment

Owner name: VERONA, INC., NEW JERSEY

Free format text: PATENT RELEASE;ASSIGNOR:JPMORGAN CHASE BANK, N.A. (F/K/A THE CHASE MANHATTAN BANK);REEL/FRAME:026930/0774

Effective date: 20110823

Owner name: ISP CAPITAL, INC., NEW JERSEY

Free format text: PATENT RELEASE;ASSIGNOR:JPMORGAN CHASE BANK, N.A. (F/K/A THE CHASE MANHATTAN BANK);REEL/FRAME:026930/0774

Effective date: 20110823

Owner name: ISP CHEMICAL PRODUCTS, INC., NEW JERSEY

Free format text: PATENT RELEASE;ASSIGNOR:JPMORGAN CHASE BANK, N.A. (F/K/A THE CHASE MANHATTAN BANK);REEL/FRAME:026930/0774

Effective date: 20110823

AS Assignment

Owner name: ASHLAND LICENSING AND INTELLECTUAL PROPERTY LLC, OHIO

Free format text: RELEASE OF PATENT SECURITY AGREEMENT;ASSIGNOR:THE BANK OF NOVA SCOTIA;REEL/FRAME:030025/0320

Effective date: 20130314

Owner name: AQUALON COMPANY, DELAWARE

Free format text: RELEASE OF PATENT SECURITY AGREEMENT;ASSIGNOR:THE BANK OF NOVA SCOTIA;REEL/FRAME:030025/0320

Effective date: 20130314

Owner name: ISP INVESTMENTS INC., DELAWARE

Free format text: RELEASE OF PATENT SECURITY AGREEMENT;ASSIGNOR:THE BANK OF NOVA SCOTIA;REEL/FRAME:030025/0320

Effective date: 20130314

Owner name: HERCULES INCORPORATED, DELAWARE

Free format text: RELEASE OF PATENT SECURITY AGREEMENT;ASSIGNOR:THE BANK OF NOVA SCOTIA;REEL/FRAME:030025/0320

Effective date: 20130314

Owner name: ASHLAND LICENSING AND INTELLECTUAL PROPERTY LLC, O

Free format text: RELEASE OF PATENT SECURITY AGREEMENT;ASSIGNOR:THE BANK OF NOVA SCOTIA;REEL/FRAME:030025/0320

Effective date: 20130314

FPAY Fee payment

Year of fee payment: 12

AS Assignment

Owner name: ISP INVESTMENTS LLC, DELAWARE

Free format text: CONVERSION;ASSIGNOR:ISP INVESTMENTS INC.;REEL/FRAME:041556/0499

Effective date: 20160818

AS Assignment

Owner name: THE BANK OF NOVA SCOTIA, AS ADMINISTRATIVE AGENT, CANADA

Free format text: SECURITY AGREEMENT;ASSIGNORS:AVOCA, INC.;HERCULES LLC;ISP INVESTMENTS LLC;AND OTHERS;REEL/FRAME:043084/0753

Effective date: 20170630

Owner name: THE BANK OF NOVA SCOTIA, AS ADMINISTRATIVE AGENT,

Free format text: SECURITY AGREEMENT;ASSIGNORS:AVOCA, INC.;HERCULES LLC;ISP INVESTMENTS LLC;AND OTHERS;REEL/FRAME:043084/0753

Effective date: 20170630

AS Assignment

Owner name: HERCULES LLC, DELAWARE

Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:THE BANK OF NOVA SCOTIA;REEL/FRAME:051557/0504

Effective date: 20200110

Owner name: AVOCA LLC, NORTH CAROLINA

Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:THE BANK OF NOVA SCOTIA;REEL/FRAME:051557/0504

Effective date: 20200110

Owner name: PHARMACHEM LABORATORIES LLC, NEW JERSEY

Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:THE BANK OF NOVA SCOTIA;REEL/FRAME:051557/0504

Effective date: 20200110

Owner name: ISP INVESTMENTS LLC, NEW JERSEY

Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:THE BANK OF NOVA SCOTIA;REEL/FRAME:051557/0504

Effective date: 20200110