Drug dissolution and transit in a heterogenous gastric chyme after fed administration: Semi-mechanistic modeling and simulations for an immediate-release and orodispersible tablets containing a poorly soluble drug.

Mathematical models that treat the fed stomach content as a uniform entity emptied with a constant rate may not suffice to explain pharmacokinetic profiles recorded in clinical trials. In reality, phenomena such as the Magenstrasse or chyme areas of different pH and viscosity, play an important role in the intragastric drug dissolution and its transfer to the intestine. In this study, we investigated the data gathered in the bioequivalence trial between an immediate-release tablet (Reference) and an orally dispersible tablet (Test) with a poorly soluble weak base drug administered with or without water after a high-fat high-calorie breakfast.

Conjunction of semi-mechanistic in vitro-in vivo modeling and population pharmacokinetics as a tool for virtual bioequivalence analysis - a case study for a BCS class II drug.

Virtual bioequivalence trial (VBE) simulations based on (semi)mechanistic in vitro-in vivo (IVIV) modeling have gained a huge interest in the pharmaceutical industry. Sophisticated commercially available software allows modeling variable drug fates in the gastrointestinal tract (GIT). Surprisingly, the between-subject and inter-occasion variability (IOV) of the distribution volumes and clearances are ignored or simplified, despite substantially contributing to varied plasma drug concentrations.

Exploiting synergistic effects of brittle and plastic excipients in directly compressible formulations of sitagliptin phosphate and sitagliptin hydrochloride.

Direct compression (DC) is the simplest and most economical way to produce pharmaceutical tablets. Ideally, it consists of only two steps: dry blending of a drug substance(s) with excipients followed by compressing the powder mixture into tablets. In this study, immediate-release film-coated tablets containing either Sitagliptin phosphate or Sitagliptin hydrochloride were developed using DC technique.

Development of a Biphasic-Release Multiple-Unit Pellet System with Diclofenac Sodium Using Novel Calcium Phosphate-Based Starter Pellets.

Novel calcium phosphate-based starter pellets were used to develop a biphasic-release multiple-unit pellet system (MUPS) with diclofenac sodium as a model drug in the form of hard gelatin capsules. For comparative purposes, corresponding formulations based on the inert cores made of microcrystalline cellulose, sucrose and isomalt were prepared. The developed system consisted of two types of drug-layered pellets attaining different release patterns: delayed-release (enteric-coated) and extended-release.

Application of Dominance-Based Rough Set Approach for Optimization of Pellets Tableting Process.

Multiple-unit pellet systems (MUPS) offer many advantages over conventional solid dosage forms both for the manufacturers and patients. Coated pellets can be efficiently compressed into MUPS in classic tableting process and enable controlled release of active pharmaceutical ingredient (APIs). For patients MUPS are divisible without affecting drug release and convenient to swallow.

The use of novel tools for the assessment of powders and granules flow properties and for the analysis of minitablets compression process.

The purpose of this study was to apply the rheological measurements to assess the flow properties of powders and granules and to compare the results with the standard pharmacopeial tests. Quality by design approach was utilized to better understand the compression of the solids into minitablets. Insights are provided regarding the methodology of rheological properties of powders and granules using powder flow analyzer (PFA).

Optimization of pellets manufacturing process using rough set theory.

Pharmaceutical pellets are spherical agglomerates manufactured in extrusion/spheronization process. The composition of the pellets, the amount of active pharmaceutical ingredient (API) and the type of used excipients have an influence on the shape and quality of dosage form. A proper quality of the pellets can also be achieved by identifying the most important technological process parameters.

Technology of eye drops containing metronidazole.

The aim of the studies was to determine the stability of metronidazole using UV spectrophotometric method in 0.5% w/w eye drops which were prepared under aseptic conditions and thermally sterilized. 0.