359회 Formulation and Evaluation of Advanced Dosage Forms for Optimal B…

359회

연사 :  이 범 진, 강원대학교 약학대학

제목: Formulation and Evaluation of Advanced Dosage Forms for Optimal Bioavailability and Clinical Therapeutics

Abstract

 Development of advanced dosage forms with optimal clinical therapeutics has been critical issue in pharmaceutical industries for marketing strategies. Because of high risk and limitation of new chemical entities, drug delivery system and modified novel drug is of continuing concern, especially in Korean pharmaceutical market. However, to design successful dosage forms, extensive understanding of physicochemical, pharmaceutical and biopharmaceutical characteristics as well as in vivo pharmacokinetics/pharamacodynamics of model compounds is required. Furthermore, pharmaceutical excipients as generally recognized as safe (GRAS) for dosage formulation must be also carefully selected. The principle of preparation of dosage forms includes many steps: 1) selection of model drug and excipients, 2) proper manufacturing process such as mixing, kneading, filling, heating, drying and tableting etc., 3) evaluation of the prepared dosage forms such as dissolution/release, disintegration, stability and pharmacokinetic behaviors etc., 4) proper packaging, 5) FDA approval 6) finally, PMS (postmarketing survey) and SUPAC (scale-up post-approval change).

Among various routes of administration, oral dosage forms are very popular in many clinical reasons. At first, sustained and controlled release dosage forms are preferable and have been widely investigated in order to reduce dosing frequency, maintain stable therapeutic effects, decrease adverse effects and increase patient compliance. Here, novel dosage form with immediate and extended release is described. In addition, new polymeric coating techniques for the controlled release are also mentioned.

Secondly, dosage forms of low soluble and low bioavailable drugs for enhanced dissolution and bioavailability are also of concern in pharmaceutical industries. The bioavailability of drugs is highly dependent on drug properties, characteristics of drug products, and patient conditions. Pharmaceutical problems of poorly water-soluble and low bioavailable drugs including low dissolution in GI tract including high P-GP efflux, high first-pass metabolism, poor in vitro/in vivo correlation (IVIVC), formulation difficulty, local gastrointestinal irritation, large intersubject variation can be commonly occurred. Solid dispersion (SD) is one of effective methods to enhance the solubility and dissolution rate of various poorly water-soluble and low bioavailable drugs. Various polymeric carriers such as polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and cellulose derivatives (HPMC, MC, HPC etc) as nontoxic, water-soluble and generally applicable pharmaceutical excipients have been widely used in the preparation of solid dispersions. In addition to, various additives such as fatty acid and surfactants can be also utilized at the same time to improve the solubility of poorly water-soluble drugs in the PVP-based solid dispersions.

®®In this presentation, advanced dosage forms of low soluble and low bioavailable drugs for enhanced dissolution and bioavailability are introduced. For example, aceclofenac (AFC) as a model has poor solubility in water and low pH conditions, resulting in lower dissolution rate and bioavailability. The AcetalⓇ capsule containing PVP-based SD showed good dissolution rate and enhanced bioavilability by forming nanoemulsion when dispersed in gastric fluid as compared with commercial AirtalⓇ tablets in spite of 70% reduced doses of AFC. The unique and novel AcetalⓇ capsule is very economical and stable during storage condition. The AcetalⓇ capsule has unique marketing strategies such as reduced gastric irritation, rapid onset time and unique dosage form. The novel premicremulsion system containing antifungal agent for the enhanced dissolution and bioavailability is also investigated and under development.

In conclusion, advanced dosage preparation strategy must initiate from beginning to end during development processes in the right time and right place. Novel concepts based extensive experiences should be motivated for obtaining future patent. Most of all, clinical advantages, patient needs and marketing strategies must be considered at the same time. However, dosage formulation and manufacturing processing should be simple as possible. Government policies such as proper drug price and approval regulations are also important.