IMPACT OF HYDROXYPROPYL METHYLCELLULOSE (HPMC) TYPE AND CONCENTRATION ON THE SWELLING AND RELEASE PROPERTIES OF PROPRANOLOL HYDROCHLORIDE MATRIX TABLETS USNING A SIMPLEX CENTROID DESIGN

Objective: To prepare hydroxypropyl methylcellulose (HPMC) matrix tablets of propranolol hydrochloride (PNL) using a simplex centroid design. Methods: HPMC matrix tablets with different amounts and types of HPMC were prepared by direct compression. A simplex centroid design was used to evaluate tablet weight (Y1), thickness (Y2), hardness (Y3), axial swelling time at 0.5–12 h (Y4-Y9), radial swelling time at 0.5–12 h (Y10-Y15), and % released at 1–12 h (Y16-Y19). Results: The tablet weight, thickness, and hardness were 397.6–400.4 mg, 3.967–4.029 mm, and 106.9–139.0 N, respectively. The % swelling (axial) and % swelling (radial) at 0.5–12 h were-8.715 to 59.889 and-1.887 to 49.287, respectively. The negative % swelling could be attributed to erosion of the tablets. The in vitro release of PNL from the tablets in buffer solution pH 1.2 (1 h) and pH 7.5 (3–12 h) was 21.12–76.22%. Tables with a high proportion of K100M HPMC had high PNL release, and the mechanism of PNL release was diffusion-and erosion-controlled. Conclusion: The simplex centroid design is potentially advantageous for formulating PNL-HPMC matrix tablets

PHYSICOCHEMICAL CHARACTERIZATION OF PROPRANOLOL-LOADED CHITOSAN NANOPARTICLES FOR A BUCCAL DRUG DELIVERY SYSTEM

Objective: This study aimed to characterize the physicochemical properties, including pH, zeta potential, and particle size of propranolol-loaded nanoparticles that were incorporated into a buccal transmucosal drug-delivery system. Methods: An ionotropic gelation technique was used to formulate propranolol-loaded chitosan nanoparticles. Chitosan used as the nanoparticle base, using tripolyphosphate (TPP) as a cross-linking agent. The effects on nanoparticle physical properties, including pH, zeta potential, and particle size were examined when various chitosan [0.150-0.300 % (w/v)] and propranolol contents (0-40 mg) were used during the preparation. The effects of using chitosan solutions with different pH values on nanoparticle properties were also determined. Results: The pH values of all nanoparticles ranged between 4.14–4.55. The zeta potentials of the prepared nanoparticles ranged between 22.6–52.6 mV, with positive charges. The nanoparticle sizes ranged from 107–140 nm, which are within the range of suitable particle sizes for transmucosal preparations. Conclusion: The pH values, zeta potentials, and particle sizes of the nanoparticle formulations were influenced by the concentrations of chitosan and propranolol and by the pH of the initial chitosan solution. The relationships between nanoparticle properties and all factors primarily depended on the ionic charges of the components, especially chitosan. Our study provides beneficial physicochemical knowledge for the further development of chitosan-based nanoparticles containing propranolol for buccal drug delivery systems

USING A SIMPLEX CENTROID DESIGN AND FATTY ACIDS TO OPTIMIZE FLUCONAZOLE-LOADED SOLID LIPID NANOPARTICLES (SLNs)

Objective: This study aimed to prepare fluconazole (FZ)-loaded solid lipid nanoparticles (SLNs) using a simplex centroid design and fatty acids to optimize the SLNs to get small-sized nanoparticles with a narrow distribution. Methods: Hot emulsification was used to prepare the FZ-loaded SLNs. Stearic acid (Sa) (X1), palmitic acid (Pa) (X2), and myristic acid (Ma) (X3) were the solid lipids. The effect of various types and amounts of fatty acids on the particle size, polydispersity index, zeta potential, and pH of the SLNs was studied using the simplex centroid design. Results: The particle size of all formulations ranged between 16.49 nm and 56.65 nm, and the polydispersity index (PDI) ranged between 0.258 and 0.676, indicating a relatively narrow size distribution. The zeta potential ranged from–7.47 to–12.2 mV. The pH was around 4.63–4.77, indicating that the SLN system was a weak acid. Design-Expert® software was used to design the responses of all model formulations and to select the optimized formulation. The optimal formulation comprised 0.190 g Sa, 0.048 g Pa, and 0.002 g Ma. The experimental values of the particle size and PDI of the optimal formulation did not differ significantly from the predicted values and lay within a 95% confidence interval (CI). Conclusion: Therefore, the simplex centroid design using fatty acids could efficiently formulate and optimize FZ-loaded SLNs

Drug-Polymers Composite Matrix Tablets: Effect of Hydroxypropyl Methylcellulose (HPMC) K-Series on Porosity, Compatibility, and Release Behavior of the Tablet Containing a BCS Class I Drug

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

Development of Triamcinolone Acetonide-Loaded Nanostructured Lipid Carriers (NLCs) for Buccal Drug Delivery Using the Box-Behnken Design

The aim of this present work was to prepare triamcinolone acetonide (TA)-loaded nanostructured lipid carriers (TA-loaded NLCs) for buccal drug delivery systems using the Box-Behnken design. A hot homogenization method was used to prepare the TA-loaded NLCs. Spermaceti (X1), soybean oil (X2), and Tween 80 (X3) were used as solid lipid, liquid lipid, and stabilizer, respectively. The particle size of TA-loaded NLCs was lower than 200 nm and the zeta potential displayed the negative charge in all formulations. The percentage encapsulation efficiency (%EE) of the TA-loaded NLCs showed that it was higher than 80% for all formulations. Field emission scanning electron microscope (FESEM) confirmed that the size of TA-loaded NLCs was approximately 100 nm and energy-dispersive X-ray spectroscopy (EDS) confirmed that the TA could be incorporated in the NLC system. The Higuchi model gave the highest value of the R2, indicating that this model was a fit for the TA release profiles of TA-loaded NLCs. Confocal laser scanning microscopy (CLSM) was used to observe the drug penetration within the porcine buccal mucosa and Nile red-loaded NLCs showed significantly higher penetration depth at 8 h than at 2 h. Therefore, TA-loaded NLCs could be an efficient carrier for drug delivery through the buccal mucosa

Thermosensitive Polymer Blend Composed of Poloxamer 407, Poloxamer 188 and Polycarbophil for the Use as Mucoadhesive In Situ Gel

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

Buccal administration of mucoadhesive blend films saturated with propranolol loaded nanoparticles

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