Effect of Adhesive Layer Thickness and Drug Loading on Estradiol Crystallization in a Transdermal Drug Delivery System

The effects of adhesive layer thickness and drug loading on estradiol crystallization were studied in a drug-in-adhesive patch. Patches containing different estradiol loadings (1.1% and 1.6% w/w) in different thicknesses (45, 60, and 90 μm) were prepared by coating of a homogenous mixture of adhesive solution and the drug on a siliconized release liner by a film applicator. After drying, the film was laminated on a Poly(ethylene terephthalate) backing layer and cut into appropriate size. Release tests were performed using thermostated Chien-type diffusion cells. Cross-section of the patches was observed by optical microscopy. Scanning electron microscopy was done for surface analysis of the patches after drug release test. Crystal formation was not expected in the adhesive layer based on the linear free-energy relationship formalisms however; crystalline regions were observed in different locations through the thickness of the patches. These regions were significantly more discontinuous in 45 μm samples which elucidated the effective role of adhesive layer thickness in drug crystallization. Extensive crystallization observed for thicker patches was attributed to the strong crosslinking capability of estradiol hemihydrate. Drug release study confirmed some of the crystallization results. No significant increase was observed in the burst release with increasing in thickness from 45 to 60 μm which can be attributed to the severe increase in the crystallization extent. Also, formation of a crystalline layer near the releasing surface and more discontinuous pattern of the crystals in some samples was confirmed by investigation of the drug release curves

Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion

The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation of its solid dispersion with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1∶9 solid dispersion with PVP K30 was used with various disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of disintegration time and percentage friability, a 32 randomized full and reduced factorial design was used to optimize the influence of the amounts of superdisintegrant and subliming agent. The obtained results showed that dispersion of the drug in the polymer considerably enhanced the dissolution rate. The drug-to-carrier ratio was the controlling factor for dissolution improvement. FTIR spectra revealed no chemical incompatibility between the drug and PVP K30. As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which explains the better dissolution rate of the drug from its solid dispersions. Concerning the optimization study, the multiple regression analysis revealed that an optimum concentration of camphor and a higher percentage of crospovidone are required for obtaining rapidly disintegrating tablets. In conclusion, this investigation demonstrated the potential of experimental design in understanding the effect of the formulation variables on the quality of mouth dissolve tablets containing solid dispersion of a hydrophobic drug

Discriminating the molecular identity and function of discrete supramolecular structures in topical pharmaceutical formulations

Copyright 2012 Elsevier B.V., All rights reserved.There is a need to understand how solvent structuring influences drug presentation in pharmaceutical preparations, and the aim of this study was to characterize the properties of propylene glycol (PG)/water supramolecular structures such that their functional consequences on drug delivery could be assessed. Shifts to higher wavenumbers in the C–H and C–O infrared stretching vibrations of PG (up to 8.6 and 11 cm–1, respectively) implied that water supramolecular structures were being formed as a consequence of hydrophobic hydration. However, unlike analogous binary solvent systems, water structuring was not enhanced by the presence of the cosolvent. Two discrete populations of supramolecular structures were evident from the infrared spectroscopy: water-rich structures, predominant below a PG volume fraction (fPG) of 0.4 (unmoving water bending vibration at 1211 cm–1) and PG-rich structures, predominant above 0.4 fPG (both C–H and water peaks moved to lower wavenumbers). The un-ionized diclofenac log–linear solubility and transmembrane transport altered dramatically when fPG > 0.55 (a 10-fold increase in transport from 0.28 ± 0.06 μg·cm–2·h–1 at 0.2 fPG to 2.81 ± 0.16 μg·cm–2·h–1 at 0.9 fPG), and this demonstrated the ability of the PG rich supramolecular structures, formed in the PG/water solvent, to specifically modify the behavior of un-ionized diclofenac.Peer reviewe

Manipulation of corticosteroid release from a transiently supersaturated topical metered dose aerosol using a residual miscible co-solvent

Purpose. The creation of supersaturation transiently after application overcomes the issue of drug instability. However, if the solvents used to drive supersaturation evaporate too quickly, drug recrystallisation or rapid film drying can occur which will inhibit drug release. As such the effects of a residual solvent, poly(ethylene glycol) 400 (PEG), on the release, mobility and supersaturation kinetics of a transiently supersaturated formulation were studied. Materials and Methods. Metered dose aerosol (MDA) formulations consisting of hydrofluoroalkane 134a, ethanol, poly(vinyl pyrrolidone) K90, beclomethasone dipropionate (BDP), and 0%, 5% or 10% w/w PEG were prepared in canisters sealed with metered dose valves and tested for release and adhesion over time. Results. The addition of 10% PEG to the MDA formulation resulted in a significant reduction (p < 0.05) in steady state drug release rate (230.4 +/- 17.3 mu g/cm(2)/h for 0% PEG MDA, 83.6 +/- 4.9 mu g/cm(2)/h for 10% PEG MDA). The presence of PEG caused a delay in dose depletion (2 h for 0% PEG MDA versus 4 h for 10% PEG), retarded supersaturation kinetics and increased film drying time. Conclusion. Whilst equivalent amounts of BDP were released, the residual solvent altered the drug release profile to achieve more constant delivery.Peer reviewe