Herein, thermosensitive blends of poloxamer 407 (P407)/poloxamer 188 (P188)/polycarbophil (PCB) were developed in terms of maximized content of PCB (a mucoadhesive polymer) and desired temperature-dependent rheological properties of the blends as in situ gelling matrices. Maximizing PCB content while achieving the preferable rheological characteristics was accomplished through the Box–Behnken design. The quantitative effect of the polymer composition in the blends on the thermosensitive characteristics was evaluated using the fitted design model and the corresponding surface plots. The optimized P407/P188/PCB blend (OPT) was the mixture of 20.000, 7.349 and 0.595% (w/w) of P407, P188, and PCB, respectively. The thermosensitive micellization of OPT was investigated using differential scanning calorimetry which revealed an overlapping double endothermic peak caused by the temperature-induced micellization of pure micelles in co-existence with the micelles with attached PCB. Mixing PCB with the P407/P188 matrix promoted a more intense mucoadhesion of the blend. After incorporating metronidazole, a model hydrophilic drug, into OPT, the temperature-dependent characteristics of the hydrogel did not change. Metronidazole release from OPT was sustained by an anomalous mechanism. This optimal ternary hydrogel benefiting from thermosensitive gelling and mucoadhesive matrix might be used as a viable platform for mucoadhesive in situ gelling drug delivery.
The purpose of this research was to see how the physicochemical properties and porosity of matrix tablets containing various types of hydroxypropyl methylcellulose (HPMC) K series affected the release of propranolol hydrochloride (PNL). PNL is a class I drug (high solubility and permeability) according to the Biopharmaceutics Classification System (BCS), making it an excellent model drug used for studying extended-release drug products. The direct compression method was used to prepare the HPMC-based matrix tablets. PNL and the excipients were found to be compatible using Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). The surfaces of all the compressed HPMC-based matrix tablets were rough, with accumulated particles and small holes. The compressed HPMC-based matrix tablet porosity was also determined by using mercury porosimetry. The compressed HPMC-based matrix tablets made of low viscosity HPMC had tiny pores (diameter < 0.01 μm). The shorter polymeric chains are more prone to deformation, resulting in a small pore proportion. The compressed HPMC-based matrix tablets sustained the release of PNL for over 12 h. The release exponent values (n), which reflect the release mechanism of the drug from the tablets, ranged from 0.476 to 0.497. These values indicated that the release was governed by anomalous transport. The compressed HPMC-based matrix tablets have the potential for a sustained release of PNL.
1 June 2021 in Journal of Drug Delivery Science and Technology