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 aims of this study were to prepare and characterize hydroxypropyl methylcellulose (HPMC)/polycarbophil (PC) mucoadhesive blend films saturated with propranolol hydrochloride (PNL)-loaded nanoparticles to improve permeability of drugs that undergo first-pass metabolism. An ionic cross-linking method and film casting technique was used to prepare nanoparticles and mucoadhesive blend films, respectively. Increasing concentrations of PNL (70, 80, 90 mg/film) in HPMC/PC blend films containing PNL-loaded nanoparticles (PN-films) and HPMC/PC blend films containing PNL (80 mg/film) without nanoparticles (PP-films) were prepared to test swelling, mucoadhesiveness, release, permeation and physicochemical properties. Scanning electron microscope (SEM) images showed a partially smooth surface with a wrinkled occurrence and spherically shaped, well-dispersed nanoparticles on the surface of PN-films containing PNL 80 mg/film (PN-films-80). The size of the nanoparticles on the surface of PN-films-80 was around 100 nm, which was similar to the nanoparticle size observed using light scattering technique. The swelling index (SI) of all PN-films and PP-films increased greatly in the first period time (10-20 min) and reached swelling equilibrium at 20 min and 30 min, respectively. For the PN-films, the concentration of PNL influenced the mucoadhesive properties and tended to be higher when the amount of PNL increased. Immediate release of all blend film formulations was found in early time points (10-30 min). After 120 min, the release of PN-films-70 was lower than the other PN-films. Permeation studies using porcine buccal mucosa showed that inclusion of nanoparticles in the films increased the permeability of PNL compared to PP-films. Therefore, buccal administration of mucoadhesive blend films containing PNL-loaded nanoparticles could be a promising approach for drugs that undergo first-pass metabolism.

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.

The objectives of this study were to prepare the hydroxypropyl methylcellulose (HPMC)/polycarbophil (PC) mucoadhesive blend film and to investigate the main and interaction effect of HPMC and PC mixtures on the physicochemical and mechanical properties of blend films using a simplex lattice mixture design approach. The cubic and quadratic models were selected to analyze mucoadhesive properties in terms of work of adhesion and maximum detachment force, respectively. It was shown that HPMC/PC blend film had higher mucoadhesive properties than pure HPMC film. The suitable models for analyzing swelling index of blend films at various times were assessed. The puncture strength, % elongation and hydrophilicity of films were also examined. The pure HPMC film displayed more homogeneous and smoother structures compared with the blend film, as observed by scanning electron microscope and atomic force microscopy. Intermolecular hydrogen bonding between HPMC and PC was detected using Fourier transform infrared and X-ray diffraction. Therefore, the blend film shows high potential for use as a buccal delivery system.