Effect of Differential Surface Anisotropy on Dissolution Behavior of Fenofibrate Crystal Habits: Comparative Study using USP Type 2 and Type 4 Dissolution Apparatuses.

The solid-state properties of active pharmaceutical ingredient (API) have significant impact on its dissolution performance. In the present study, two different crystal habits viz. rod and plate shape of form I of FEN were evaluated for dissolution profile using USP Type 2 and Type 4 apparatuses. Molecular basis of differential dissolution performance of different crystal habits was investigated. Rod (FEN-R) and plate (FEN-P) shaped crystal habits of Form I of FEN were generated using anti-solvent crystallization method. Despite the same polymorphic form and similar particle size distribution, FEN-P demonstrated higher dissolution performance than FEN-R. Crystal face indexation and electrostatic potential (ESP) map provided information on differential relative abundance of various facets and their molecular environment. In FEN-R, the dominant facet (001) is hydrophobic due to the exposure of chlorophenyl moiety. Whereas, in FEN-P the dominant facet (01-1) was hydrophilic due to the presence of chlorine and ester carbonyl groups. Deeper insight on the impact of different facets on dissolution behavior was obtained by energy framework analysis by unveiling strength of intermolecular interactions along various crystallographic facets. Moreover, type 4 apparatus provided higher discriminatory ability over USP Type 2 apparatus, in probing the crystal habit induced differential dissolution performance of FEN. The findings of this study emphasize that crystal habit should be considered as an important critical material attribute (CMA) during formulation development of FEN and due considerations should be given to the selection of the appropriate dissolution testing set-up for establishing in vitro-in vivo correlation.

The effect of alcohol on ionizing and non-ionizing drug release from hydrophilic, lipophilic and dual matrix tablets.

The aim of this work was to investigate and quantitatively evaluate the effect of presence of alcohol on in vitro release of ionizing and non-ionizing drug from hydrophilic, lipophilic and hydrophilic-lipophilic matrix tablets. The Food and Drug Administration (FDA) recommends in vitro dissolution testing of extended release formulations in ethanolic media up to 40% because of possible alcohol-induced dose dumping effect. This study is focused on comparison of the dissolution behavior of matrix tablets (based on hypromellose and/or glyceryl behenate as retarding agent) of the same composition containing different type of drug - ionizing tramadol hydrochloride (TH) and non-ionizing pentoxifylline (PTX). The dissolution tests were performed in acidic medium (pH 1.2) and in alcoholic medim (20%, 40% of ethanol) and the changes of tablets were observed also photographically. It was found that the alcohol resistence of the hydrophilic-lipophilic formulations with TH and the hydrophilic-lipophilic formulations with PTX containing a higher amount of hypromellose does not reflect the alcohol resistence of the formulations with pure hypromellose or glyceryl behenate. Both hydrophilic-lipophilic formulation with TH and more lipophilic formulation with PTX show significant alcohol dose dumping effect.

Comparison of three dissolution apparatuses for testing calcium phosphate pellets used as ibuprofen delivery systems.

Porous calcium phosphate pellets were produced according to two granulation processes (low and high shear wet granulations) and drug loaded with five ibuprofen contents (1.75%, 7%, 12.5%, 22%, and 36%) in order to ensure both bone defect filling and local drug delivery. The drug-release kinetics from the two types of pellets was studied using three dissolution apparatuses: paddle apparatus, reciprocating cylinder, and flow-through cell. The paper compared the three dissolution methods and considered the effect of the granulation process on the ibuprofen-release kinetics. Dissolution data were analyzed using the Weibull function as well as the difference (f1) and similarity (f2) factors. Dissolution kinetics was not influenced by the granulation process, regardless of the dissolution apparatus and of the drug content. The comparison of the three dissolution devices indicated that ibuprofen was released faster from granules loaded with 36% of drug content with the reciprocating apparatus, due to the disintegration of the granules occurring during the dissolution test. For the other drug contents, dissolution profiles were not significantly different from one apparatus to another. However, the flow-through cell seemed to be more suitable for the drug-release study of implantable materials.