Monitoring of drug release kinetics from thin polymer films by multi-parametric surface plasmon resonance.

The aim of the present study is to monitor the release of perphenazine (PPZ) from thin polymer films in real-time by the multi-parametric surface plasmon resonance method (MP-SPR). The MP-SPR method is capable of measuring changes in polymer films that are significantly thicker than the apparent scanning depth of the SPR field. The in vitro reference measurements confirm that the MP-SPR results can be correlated to the in vitro release of PPZ. However, information gained by MP-SPR can be used to identify three different modes of change in the films with different kinetic timescales, which are not visible in the in vitro testing. The EUDRAGIT(®) RL PO-PVP-PPZ-film shows significantly faster changes than the film without polyvinylpyrroline (PVP). This information can be used to optimize the drug-release profile of different film formulations for different pharmaceutical purposes.

Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets.

Continuous manufacturing gains more and more interest within the pharmaceutical industry. The International Conference of Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product performance over a range of raw material attributes, manufacturing process options and process parameters. This fits further into the Process Analytical Technology (PAT) and Quality by Design (QbD) framework. The present study evaluates the effect of variation in critical raw material properties on the critical quality attributes of granules and tablets, produced by a continuous from-powder-to-tablet wet granulation line. The granulation process parameters were kept constant to examine the differences in the end product quality caused by the variability of the raw materials properties only. Theophylline-Lactose-PVP (30-67.5-2.5%) was used as model formulation. Seven different grades of theophylline were granulated. Afterward, the obtained granules were tableted. Both the characteristics of granules and tablets were determined. The results show that differences in raw material properties both affect their processability and several critical quality attributes of the resulting granules and tablets.

Detection of porosity of pharmaceutical compacts by terahertz radiation transmission and light reflection measurement techniques.

We report on the non-destructive quantification of the porosity of pharmaceutical compacts (microcrystalline cellulose tablets) by using both optical and terahertz techniques. For the full analysis of the porosity of pharmaceutical tablets, the results obtained in both cases have shown that optical and terahertz techniques are complementary. The intrinsic refractive index of microcrystalline cellulose was estimated using the effective refractive index obtained from the time delay of the THz pulse together with the Bruggeman model for effective media. Once this intrinsic refractive index is known, the unknown porosity of the tablet can be estimated with the aid of the measured effective refractive index as well as the thickness of the pharmaceutical tablet. The method was tested using a set of thirteen tablets having different porosities. It is shown that the error in the estimation of the unknown tablet's porosity is less than 1%. In addition, surface roughness was measured by using an optical interferometer and gloss by using a diffractive-optical-element based glossmeter. The measurement was achieved by scanning the tablets with a probe beam and detecting the reflected light. The surface roughness and gloss data show relatively good correlation with the porosities of the tablets.

Intraorally fast-dissolving particles of a poorly soluble drug: preparation and in vitro characterization.

In this study, the dissolution rate of a poorly soluble drug, perphenazine (PPZ) was improved by a solid dispersion technique to permit its usage in intraoral formulations. Dissolution of PPZ (4 mg) in a small liquid volume (3 ml, pH 6.8) within one minute was set as the objective. PVP K30 and PEG 8000 were selected for carriers according to the solubility parameter approach and their 5/1, 1/5 and 1/20 mixtures with PPZ (PPZ/polymer w/w) were prepared by freeze-drying from 0.1 N HCl solutions. The dissolution rate of PPZ was improved with all drug/polymer mixture ratios compared to crystalline or micronized PPZ. A major dissolution rate improvement was seen with 1/5 PPZ/PEG formulation, i.e. PPZ was dissolved completely within one minute. SAXS, DSC and XRPD measurements indicated that solid solutions of amorphous PPZ in amorphous PVP or in partly amorphous PEG were formed. DSC and FTIR studies suggested that PPZ dihydrochloride salt was formed and hydrogen bonding was occurred between PPZ and the polymers. It was concluded that molecular mixing together with salt formation promoted the dissolution of PPZ, especially in the case of the 1/5 PPZ/PEG dispersion, making it a promising candidate for use in intraoral formulations.

Modifying drug release and tablet properties of starch acetate tablets by dry powder agglomeration.

In this study three model drugs (N-acetyl-D-glucosamine (NAG), anhydrous caffeine, and propranolol hydrochloride) were agglomerated with starch acetate (SA) by mixing the binary powders on a stainless steel (SS) plate. Agglomeration was induced by triboelectrification of the particles during mixing, and it was evaluated as a method to achieve controlled drug release rate. These agglomerates, mixed with different amounts of a disintegrant, were compressed into tablets whose dissolution characteristics were determined. Triboelectric measurements showed that when the drugs were in contact with SS, charges of the opposite polarity were generated to SA (+) and caffeine and NAG (-) promoting adhesion. Instead, propranolol HCl was charged with the same polarity as SA. SEM micrographs showed that smaller caffeine particles, in spite of their larger negative charge, agglomerated less efficiently with SA than larger NAG particles. This emphasizes the importance of particle size in the agglomeration process. Propranolol HCl did not form agglomerates with SA since their particle sizes and charges were identical. As a result, agglomeration of powders prior to tablet compression allows for modification and control of the release rate of the drugs from the SA matrix tablets as well as the tensile strength of the tablets.