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The objective of this research was to optimize the tasted-masked microparticles for orally disintegrating tablets containing donepezil hydrochloride using quality risk assessment and design of experiment approaches. The double emulsion solvent evaporation technique using aminoalkyl methacrylate copolymer (AMC) was used to prepare taste-masked microparticles. Factors affecting the quality of the taste-masked microparticles were analyzed using an Ishikawa diagram. A risk-ranking approach was used to rank the formulation and process risks. Furthermore, the effect of AMC quantity, stirring time, and volume of outer water phase on various responses, such as particle size, the amount of drug dissolved at 5 min (Q5) in simulated saliva fluid, and mean dissolution time (MDT) in simulated gastric fluid, was investigated using the Box-Behnken design. The optimized microparticles were then used to prepare orally disintegrating tablets (ODTs) and evaluated by in vitro and in vivo testing. The results demonstrated that particle size was influenced by the AMC amount and stirring time. Q5 was significantly affected by the amount of AMC and the volume of the outer water phase. On the other hand, these two factors had a positive effect on MDT. The optimized microparticles had a particle size of 174.45 ± 18.19 µm, Q5 of 5.04%, and MDT of 5.97 min. The ODTs with taste-masked microparticles showed acceptable in vitro dissolution with an MDT of 5 min. According to the results of a panel of six human volunteers, they greatly improved palatability.

The volume and distribution of fluids available in the gastrointestinal (GI) tract may substantially affect oral drug absorption. Magnetic resonance imaging (MRI) has been used in the past to quantify these fluid volumes in adults and its use is now being extended to the pediatric population. The present research pursued a retrospective, explorative analysis of existing clinical MRI data generated for pediatric patients. Images of 140 children from all pediatric subpopulations were analyzed for their resting GI fluid volumes in fasting conditions. In general, an increase in fluid volume as a function of age was observed for the stomach, duodenum, jejunum, and small intestine (SI) as a whole. No specific pattern was observed for the ileum and colon. Body mass index (BMI), body weight, body height, and SI length were evaluated as easy-to-measure clinical estimators of the gastric and SI fluid volumes. Although weight and height were identified as the best estimators, none performed ideally based on the coefficient of determination (R2). Data generated in this study can be used as physiologically relevant input for biorelevant in vitro tests and in silico models tailored to the pediatric population, thereby contributing to the efficient development of successful oral drug products for children. ispartof: PHARMACEUTICS vol:14 issue:9 ispartof: location:Switzerland status: published

Proton-pump inhibitors (PPIs), frequently prescribed to lower gastric acid secretion, often exert an effect on the absorption of co-medicated drug products. A previous study showed decreased plasma levels of the lipophilic drug ritonavir after co-administration with the PPI Nexium (40 mg esomeprazole), even though duodenal concentrations were not affected. The present study explored if a PPI-induced decrease in gastrointestinal (GI) fluid volume might contribute to the reduced absorption of ritonavir. In an exploratory cross-over study, five volunteers were given a Norvir tablet (100 mg ritonavir) orally, once without PPI pre-treatment and once after a three-day pre-treatment with the PPI esomeprazole. Blood samples were collected for eight hours to assess ritonavir absorption and magnetic resonance imaging (MRI) was used to determine the gastric and duodenal fluid volumes during the first three hours after administration of the tablet. The results confirmed that PPI intake reduced ritonavir plasma concentrations by 40%. The gastric residual volume and gastric fluid volume decreased by 41% and 44% respectively, while the duodenal fluid volume was reduced by 33%. These data suggest that the PPI esomeprazole lowers the available fluid volume for dissolution, which may limit the amount of ritonavir that can be absorbed. Although additional factors may play a role, the effect of PPI intake on the GI fluid volume should be considered when simulating the absorption of poorly soluble drugs like ritonavir in real-life conditions. ispartof: PHARMACEUTICS vol:12 issue:7 ispartof: location:Switzerland status: published

Given the limited number of materials available to design delivery platforms for nutrients, the rational combination of raw materials already approved as food ingredients and their processing through nano-micro technology can offer a unique tool for innovation. Here, we propose a nano-in-micro strategy to produce powders based on the hydrophobic protein zein, useful for the oral delivery of a hydrophilic iron source (iron bisglycinate) in anaemic patients. Iron-loaded powders were prepared through a two-step strategy consisting in the formation of a zein pseudolatex followed by a spray-drying step. To extend the manipulation space for zein and entrap iron bisglycinate, &beta, cyclodextrin (&beta, CD) was selected as helping excipient. Addition of &beta, CD allowed iron loading in the pseudolatex and greatly increased product yields after the drying process as compared to zein alone. Iron-loaded micro-sized powders were characterised by attenuated total reflectance&ndash, Fourier transform infrared (ATR-FTIR) spectra, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) to elucidate the role of &beta, CD as a compatibilizer for the zein&ndash, iron system. Remarkably, micropowders released only 20% of FeBIS in a simulated gastric fluid, whereas release in a simulated intestinal fluid was almost completed in 7 h. In summary, &beta, CD association to zein is a novel strategy to expand applications in the oral delivery of iron bisglycinate and, prospectively, to micronutrient chelates.

In this study, we aimed to design a highly swellable and mechanically robust matrix tablet (SMT) as a gastroretentive drug-delivery system (GRDDS) capable of improving the dissolution behavior of &beta, lapachone with low aqueous solubility. For the preparation of SMTs, the cogrinding technique and freeze&ndash, thaw method were used to disperse &beta, lapachone in SMTs in an amorphous state and to enhance the swelling and mechanical properties of SMTs, respectively. As a result, the crystallinity of coground &beta, lapachone incorporated in the SMTs was found to be considerably decreased, thereby, the dissolution rates of the drug in a simulated gastric fluid could be substantially increased. The SMTs of &beta, lapachone also demonstrated significantly enhanced swelling and mechanical properties compared to those of a marketed product. The reason for this might be because the physically crosslinked polymeric networks with a porous structure that were formed in SMTs through the freeze&ndash, thaw method. In addition, &beta, lapachone was gradually released from the SMTs in 6 h. Therefore, SMTs of &beta, lapachone developed in this study could be used as GRDDS with appropriate swelling and mechanical properties for improving the dissolution behavior of hydrophobic drugs such as &beta, lapachone.