CS267045B1 - Method of isobutyl prophene containing solid medicamentous forms production - Google Patents

Abstract

Solid dosage forms comprising ibuprofen is prepared by granulating the mixture active ingredients and excipients and tableting the resulting tablet material so that adding the lubricant to the prepared wet granulate in the mold solution in an organic solvent, preferably an acid solution is used stearic in ethyl alcohol.

Description

Tablets are the most common dosage form ever. They have a mechanically stable structure which, however, must break up on contact with water or body fluids and the tablets must disintegrate into granular grains and particles formed from them. These particles must then allow the active substance to pass into solution. The release of the active substance from the preparation and its transition from the physical system of the dosage form to the biological system of the organism depends on many factors. The main limiting factor for oral bulk drugs is the rate of dissolution. Factors affecting the dissolution process and thus the bioavailability are either variables of the technological process or variables of the materials used in the creation and production of the medicinal product. At the same time, it is necessary to realize that considerable requirements, sometimes contradictory, are placed on the final product. The tablets must be shape-stable, mechanically resistant and strong, resistant to air humidity, but in contact with water they must disintegrate into starting components which must dissolve quickly enough and must be chemically stable. They are prepared by compressing a so-called tablet, which consists of a mixture of active ingredients with excipients which impart properties to the tablet so as to be suitable for tableting on rotary tablet presses, such as sufficient flowability, homogeneity of the mixture and non-stickiness of the mixture and non-stickiness of the mixture maintaining sufficient mechanical strength. Sometimes and exceptionally, tablets can be produced directly by compressing a homogeneous mixture obtained by mixing dustable active ingredients and excipients. More often than before tableting, the powdered substance must be bonded with a suitable binder in the wet way, compacted and prepared from them into a granulate with suitable properties for tableting and only compressed after the possible addition of other excipients.

Various excipients are used to prepare the granules. Fillers are pharmacologically indifferent substances that supplement the active substances so that the mixture is workable, binders ensure the formation of granular grains from dust particles and also their cohesiveness, lubricants allow good flowability of the tablet and at the same time cause compression mandrels in tablet matrices even if the tablets do not stick to the punches, the disintegrants ensure the disintegration of the tablet into particles in the required time in the digestive tract.

Various technologies can be used to produce granules. It is possible to work in dry conditions, where the dust particles are compacted by the action of high pressure or by grinding the dust particles with a solution of binders. Wet granulation can be made by kneading, in which a plastic mass is formed from the dust particles and the binder solution, which is mechanically crushed and the resulting grains are dried or by direct aggregation of the particles in suspension.

When creating a recipe and determining a suitable technological procedure, it is necessary to take into account the mutual compatibility of the individual components, both active and auxiliary substances. .

One of the most difficult cases of prescriptions are solid controlled release dosage forms with the required bioavailability. Such cases include various analgesic, anti-rheumatic and anti-inflammatory tablets containing ibuprofen. These tablets are required to disintegrate the tablet as quickly as possible and to convert the active ingredient into solution as quickly as possible while maintaining the requirement for tablet strength and compressibility.

Due to the fact that ibuprofen is a substance with a large specific surface area, the addition of glidants added when dry proved to be ineffective, so there was backfilling or sticking to dies, and with a higher content of these substances there was a significant slowdown of disintegration and release rate. .

CS 267 045 Bl

If, in addition to the binder, a lubricant solution is used in the granulation of ibuprofen so that, after evaporation of the solvent, a thin film is formed on the surface of these granules, then the physicochemical properties of the ibuprofen-containing granules are ideal for tableting.

Based on the acquired knowledge and experimental results of monitoring the rate of ibuprofen release against the content and method of application of lubricants to or on the granulate, a method for the production of stable ibuprofen-containing oral dosage forms for controlled release oral administration from pre-prepared granules was developed by: tablets the granulate with a mixture of active substance and excipients in such a way that a glidant, preferably atearic acid, is added to the prepared wet granulate in the form of a solution in an organic solvent. The lubricant is added in an amount of 0.5 to 2% by weight based on the weight of the dry granulate. Preferably, a solution of stearic acid in ethyl alcohol is used in a concentration of from 15 to 35% by weight.

The invention is further elucidated in the following example:

Example

A homogeneous mixture of 400 kg of ibuprofen, 125.75 kg of starch and 37.25 kg of pregelatinized starch is prepared. 171.5 kg of water are poured onto this mixture and the mixture is granulated in a high-speed granulating device. A solution of 8 kg of stearic acid dissolved in 23 kg of ethyl alcohol is poured onto the wet granulate thus formed. The resulting mixture is mixed, the granulate is dried and sieved. Additional tableting ingredients are added to the granulate, namely 8 kg of talc, kg of aerosol and 18 kg of ultraamylopectin. After homogenization, the resulting tablet is tableted on high-performance rotary tablet presses to obtain tablets weighing 600 mg. The tablets thus prepared, despite any further coating with a layer of hydroxypropylmethylcellulose, release at least 50% of the active ingredient within 30 minutes under the prescribed conditions.

Claims (2)

PRIORITY OF THE INVENTION A process for the preparation of solid dosage forms containing ibuprofen by granulating a mixture of active ingredient and excipients and tablet-prepared tablet, characterized in that a lubricating excipient, for example stearic acid, is added to the prepared wet granulate in the form of a solution in an organic solvent in an amount of 0. , 5 to 2% by weight based on the weight of the dry granulate. 2. The process according to item 1, characterized in that a solution of stearic acid in ethyl alcohol in a concentration of 15 to 35% by weight is used.