Development Of Mebeverine Hcl Prolonged Release Mini-Tablets By Thermoplastic Granulation Technique

Mebeverine HCl is a BCS class-I drug and thus it possesses high solubility in aqueous media across the biological pH range. The marketed reference product is a multi-unit particulate system (MUPS) containing prolonged release pellets filled in hard gelatin capsule. In conventional manufacturing process, a huge quantity of solvents (aqueous and/or organic) is used to manufacture such dosage form. Additionally, it demands more processing time and efforts. Therefore, a prolonged release capsules dosage form of Mebeverine HCl was formulated using thermoplastic (melt) granulation technique without usage of any solvent. Prolonged release minitablets sized 2 mm in diameter were developed as per quality by design principles. A 23 full-factorial design of experiment was applied to optimize levels of drug release controlling ingredients which includes a hydrophobic meltable binder (hydrogenated castor oil) cum matrixing agent, a hydrophilic meltable binder (polyethylene glycol) which may act as pore former also, and a release controlling polymer (ethyl cellulose). The optimized formulation was found stable. Dissolution profiles of the optimized formulation were found similar to the marketed reference product in different media across the physiological pH range. In conclusion, the explored solvent less process was capable to manufacture the MUPS dosage form of Mebeverine HCl prolonged-release capsules, which is stable and pharmaceutically equivalent with the reference product. The developed process is more beneficial to small and medium scale industry, as it does not require any special and costly equipment, significantly decreases manufacturing cost and increases productivity compared to conventional process, which is mentioned in literature.

Research Progress of Granulation Technology for Taste Masking of Pharmaceutical Preparation / 中国实验方剂学杂志

In commonly used oral solid preparations, poor mouthfeel results in poor patient compliance with the drug, which in turn reduces the market competitiveness of the drug. The problem of taste masking of pharmaceutical preparations has always been one of the important problems faced by pharmaceutics. With the increasing demand for the taste of drugs, the methods of masking bad taste of drugs have gradually increased in recent years. By summarizing the relevant literature covering the bad taste of drugs, the commonly used taste masking techniques include the addition of taste masking agents, inclusion techniques, microsphere/microcapsule technology, solid dispersion technology, ion exchange technology and the like. However, in addition to the above taste masking techniques, in the manufacturing process of the solid preparation, the granulation technique also can achieve the shielding of the bad taste of the medicine, and the granulation technique is simple, and can well achieve the effect of masking the bad taste of the medicine. This paper systematically introduces the research progress of granulation technology in drug taste masking, in order to provide reference for the selection of drug taste masking technology. With the increasing demand for drug taste, drug masking technology has been paid more and more attention by the majority of preparation workers, however, there are still some problems, such as imperfect taste evaluation system and low specificity of methods. This series of problems need to be further studied and solved by relevant pharmaceutical researchers.

Development of Hydrophobic Carriers based tablets for Sustained Release of Verapamil.

The main aim of the study is to formulate sustained release matrix tablets of verapamil hydrochloride using hydrophobic carriers or meltable binders like stearic acid, carnauba wax and bees wax by melt granulation technique. The influence of a hydrophilic polymer like polyethylene glycol (PEG) was studied on the waxy matrices. Two grades of PEG (4000 and 6000) were used in the preparations. The granules were prepared and compressed into tablets and they are evaluated for their physicochemical properties and in vitro dissolution studies were done. The IR spectral analysis revealed that there are no interactions between drug and the polymers and are compatible with other. The release data were subjected to various release kinetic models and also compared with those of a commercial brand. The tablets prepared fulfilled all the official requirements according to the pharmacopeia. From the dissolution studies it was observed that carnauba wax acts a good retardant (more than 16 h). Among the two grades of PEG used 4000 and 6000, PEG 6000 increases the drug release to a greater extent than PEG 4000. It was concluded that hydrophobic carriers which act as very good retardants of the drug and also PEG can be used as a channeling agent in waxy matrices to regulate the release of the drug.

Application of multivariate techniques in the evaluation of melt granulation products

In this work, principal component analysis and cluster analysis were applied as helping tools to extract useful information in the development of formulations and manufacturing processes of melt granulates. Two melt granulation processes that differ in the shear stress applied to the solid bed during melting step were designed. These processes employ equipment frequently used in the local pharmaceutical industry. The selected binders include both hydrophilic and hydrophobic excipients, which were used alone or in binary mixtures. Granulates were characterized regarding their physicomechanical properties, including their compaction behavior. The resulting tablets were also evaluated. The selected multivariate statistical methods proved to be useful in facilitating the interpretation of the collected data and the study of the properties of granulates and tablets, as well as the selection of more efficient production processes.

Neste trabalho, foram aplicadas as técnicas de análise de componentes principais e de análise de agrupamentos para extrair informações úteis no desenvolvimento de formulações e de processos de produção de granulados por fusão. Desenharam-se dois processos de granulação por fusão que apresentam diferenças na tensão de cisalhamento aplicada ao leito sólido durante a etapa de fusão. Esses processos empregam equipamentos frequentemente usados na indústria farmacêutica local. Os ligantes escolhidos incluíram excipientes tanto hidrofílicos quanto hidrofóbicos, utilizados de forma individual ou em misturas binárias. Os granulados foram caracterizados quanto às suas propriedades físico-mecânicas, incluindo seu desempenho no processo de compactação. Os comprimidos resultantes também foram avaliados. Os métodos de análise multivariada escolhidos provaram ser úteis para facilitar a interpretação dos dados coletados e o estudo das propriedades dos granulados e dos comprimidos, bem como a seleção de processos de produção mais eficientes.