Preparation of medicines for children - a hierarchy of classification.

There is some confusion about the types of paediatric pharmaceutical preparation (in a regulatory and pharmaceutical development context) that are acceptable for approval by medicines regulators. Some of the confusion relates to terminology which may mean different things to different stakeholders. It may not always be possible to provide authorised, commercially manufactured, age appropriate, ready-to-administer preparations.

Low dose lipid formulations: effects on gastric emptying and biliary secretion.

Purpose: Food stimulates changes to gastrointestinal secretion and motility patterns, however, the effect of smaller quantities of lipid, such as that contained in a lipid-based drug formulation, has not been detailed. This study aimed to examine the effects of small quantities of lipid on gastric emptying and biliary secretion.

Methods: The influence of oral administration of three lipid-based formulations and a negative control formulation on gastric emptying and biliary secretion was evaluated in 16 healthy male subjects using gamma scintigraphy, ultrasonography and duodenal aspiration.

Simulation of fasting gastric conditions and its importance for the in vivo dissolution of lipophilic compounds.

In this study, the importance of accurate simulation of fasting gastric environment for the assessment of the absorption process of two model lipophilic compounds, GR253035X (weak base) and atovaquone (non-ionizable), was assessed. Dissolution profiles were constructed in previously proposed simulated gastric fluids and in a new medium that comprises only of components that have been recovered from the fasting stomach. Dissolution data obtained in a more physiologically relevant medium led to better correlation between the simulated and actual intralumenal dissolution vs.

Media to simulate the postprandial stomach I. Matching the physicochemical characteristics of standard breakfasts.

To better predict food effects on the bioavailability/bioequivalence of drugs and drug products from in-vitro data, a dissolution medium that simulates the initial composition of the postprandial stomach was developed. First, the physical parameters of two homogenized standard breakfasts often administered to assess food effects in pharmacokinetic studies were measured. These included pH, buffer capacity, osmolality, surface tension and viscosity.

Physical stability and enthalpy relaxation of drug-hydroxypropyl methylcellulose phthalate solvent change co-precipitates.

The poorly water-soluble drug GWX was co-precipitated with hydroxypropyl methylcellulose phthalate (HPMCP) using a solvent change method. The two co-precipitate formulations made, with drug-HPMCP ratios of 2:8 and 5:5, were analysed using modulated temperature differential scanning calorimetry. They were found to consist of completely amorphous solid solution and a mixture of amorphous solid solution, crystalline drug and amorphous drug, respectively.

Factors affecting incorporation of drug into solid solution with HPMCP during solvent change co-precipitation.

Drug-hydroxypropyl methylcellulose phthalate (HPMCP) mixtures were completely dissolved in acetone, and the resulting solution was added drop-wise into HCl(aq). Resulting co-precipitates were filtered, and then dried under vacuum at 45 degrees C, -800 mbar for 24 h. Modulated differential scanning calorimetry, thermogravimetric analysis, X-ray powder diffraction and HPLC were used to detect and quantify different phases present in co-precipitates.

Solvent change co-precipitation with hydroxypropyl methylcellulose phthalate to improve dissolution characteristics of a poorly water-soluble drug.

Research compound GWX belongs to biopharmaceutical classification system type II, and hence shows dissolution-rate-limited absorption. To improve its dissolution performance, GWX was formulated as a co-precipitate with hydroxypropyl methylcellulose phthalate (HPMCP). Co-precipitates with various drug-HPMCP ratios were prepared and characterised using modulated differential scanning calorimetry (MDSC), X-ray powder diffraction, HPLC and dissolution testing.