Simple Controlled Release Delivery System for an Anti-hypertensive Drug via Buccal Route.

Objective: This study aims to develop controlled release buccal tablets of losartan potassium based on bioadhesion using direct compression technique. Materials and Methods: The bioadhesive buccal tablets of losartan potassium were prepared after preliminary drug-excipients compatibility studies and micromeretics study for powder blends. The tablets were prepared by direct compression utilizing carbopol 934LR as a primary bioadhesive polymer either with or without chitosan or hydroxypropyl methylcellulose E15LV as secondary polymers. Other excipients included PVP K30 as a binder, magnesium stearate as a lubricant and mannitol as a diluent. The tablets were evaluated for weight variation, thickness and diameter, hardness, friability, drug content, surface pH, Ex-vivo residence time and bioadhesion force, In-vitro swelling and drug release study. The analysis of the release profiles in the light of distinct kinetic models (zero order, first order, Higuchi, Hixson-Crowell and Korsmeyer–Peppas) was carried out. Results and Discussion: The formula containing 40% w/w bioadhesive polymers of carbopol 934LR and chitosan (1:2) was selected as the optimum one based on a ranking methodology and then, it was subjected to Ex-vivo permeation and physical stability study in human saliva. Swelling index was 78.32±1.84% after 7h and tablets showed a neutral surface pH. Ex-vivo residence time was long enough for more than 10h. Ex-vivo bioadhesion force was 0.38±0.01N. Drug release was 57.64±3.43% after 8h following zero order kinetics with a steady state permeation flux of 0.959mg/cm2h. Tablets were physically stable in human saliva. Conclusion: These formulae improved, controlled and prolonged the release of losartan potassium from a buccal bioadhesive system for at least 8h in a simple way which can achieve a high patient compliance.

Preparation and Characterization of Polymeric Mucoadhesive Film for Buccal Administration.

Objectives: Buccal films consist mainly of polymer that has a good mucoadhesive profile and plasticizer. A lot of polymers and plasticizers can be used to configure the mucoadhesive films as hydroxyethyl cellulose and glycerin respectively. Material and Methods: Films prepared by dispersing the polymer, mixing it with plasticizer and pouring it in Petri dishes to be dried and cut finally. Physicochemical tests were used to evaluate the films. These tests are organoleptic evaluation and polymer and plasticizer selection, determination of rheological properties of polymers, film thickness, and determination of moisture content, determination of moisture uptake and evaluation of mechanical properties. Results and Conclusions: It was found that films prepared from polyvinyl alcohol 2% (w/w) especially with the addition of propylene glycol 20% from the weight of the polymer have excellent characteristics. This formula has promising organoleptic and mechanical properties and its solution is Non-Newtonian pseudoplastic. Moreover, this formula is very thin and has moderate percent of moisture content and moisture uptake. Also, it has high elongation with moderate tensile strength. As a result, it is better to prepare the film by these ingredients to obtain an ideal mucoadhesive formula.

Optimization of Gabapentin Release and Targeting Absorption, Through Incorporation into Alginate Beads.

Aims: 1) To study the effect of some formulation variables on drug load, encapsulation efficiency, swelling ratio, mucoadhesion and drug release. 2) Optimize the mucoadhesion capabilities for targeting drug absorption and release-controlling capabilities of alginate beads. Methodology: Alginate beads were prepared by dripping sodium alginate gel into calcium chloride solution and then dried overnight at ambient temperature. The effects of alginate concentration, cross linker concentration, cross linking time, volume of cross linking solution and drug/polymer ratio on drug load, encapsulation efficiency, swelling ratio, mucoadhesion and drug release were investigated. Formulae containing sodium lauryl sulfate (SLS), gabapentin-ethylcellulose solid dispersion, mixture of free drug and solid dispersion were prepared for modifying the drug release rate. Results: Mucoadhesion of alginate beads was shown to be decreased upon adding SLS (30% after 8 hrs). Drug release was so fast (92.46% after 2 hrs). The incorporation of solid dispersion has led to well accepted mucoadhesion (74.44% after 8 hrs) as well as release properties (93.35% after 10 hrs) Beads containing mixtures of drug and ethylcellulose-drug solid dispersion showed acceptable mucoadhesion (74.44% after 8 hrs) and control of gabapentin release (93.35% after 10 hrs). Statistical analysis of variance between groups was performed using the one-way layout ANOVA with duplication. Significant differences in mean values were evaluated by Student's unpaired t test (P < 0.05). Conclusion: A finally optimized formula was suggested by incorporating a combination of solid dispersion and free gabapentin in alginate system to achieve burst release of gabapentin and hence fast effect (33.417% was released during the first 30 minutes in fasting-simulated conditions) and controlled release (91.217% after 6 hrs).

Design and Characterization of Glyceryl Monostearate Solid Lipid Nanoparticles Prepared by High Shear Homogenization.

Aims: The aim of this study was to explore the practicability of preparation of solid lipid nanoparticles of Glyceryl monostearate containing Dibenzoyl peroxide, Erythromycin base, and Triamcinolone acetonide as model drugs. The physicochemical properties of the prepared formulae like particle size, drug entrapment efficiency, drug loading capacity, yield content and in-vitro drug release behavior were also measured. Methodology: Solid lipid nanoparticles loaded with three model lipophilic drugs were prepared by high shear hot homogenization method. The model drugs used are Dibenzoyl peroxide, Erythromycin base, and Triamcinolone acetonide. Glyceryl monostearate was used as lipid core; Tween 20 and Tween 80 were employed as surfactants and lecithin as co-surfactant. Many formulation parameters were controlled to obtain high quality nanoparticles. The prepared solid lipid nanoparticles were evaluated by different standard physical and imaging methods. The efficiency of drug release form prepared formulae was studied using in vitro technique with utilize of dialysis bag technique. The stability of prepared formulae was studied by thermal procedures and infrared spectroscopy. Results: The mean particle diameter measured by laser diffraction technique was (194.6±5.03 to 406.6±15.2 nm) for Dibenzoyl peroxide loaded solid lipid nanoparticles, (220±6.2 to 328.34±2.5) nm for Erythromycin loaded solid lipid nanoparticles and (227.3±2.5 to 480.6±24) nm for Triamcinolone acetonide loaded solid lipid nanoparticles. The entrapment efficiency and drug loading capacity, determined with ultraviolet spectroscopy, were 80.5±9.45% and 0.805±0.093%, for Dibenzoyl peroxide, 96±11.5 and 0.96±0.012 for Triamcinolone acetonide and 94.6±14.9 and 0.946±0.012 for Erythromycin base respectively. It was found that model drugs showed significant faster release patterns when compared with commercially available formulations and pure drugs (p˂0.05). Thermal analysis of prepared solid lipid nanoparticles gave indication of solubilization of drugs within lipid matrix. Fourier Transformation Infrared Spectroscopy (FTIR) showed the absence of new bands for loaded solid lipid nanoparticles indicating no interaction between drugs and lipid matrix and being only dissolved in it. Electron microscope of scanning and transmission techniques indicated sphere form of prepared solid lipid nanoparticles with smooth surface with size below 100 nm. Conclusions: Solid lipid nanoparticles with small particle size have high encapsulation efficiency, and relatively high loading capacity for Dibenzoyl peroxide, Erythromycin base, and Triamcinolone acetonide as model drugs can be obtained by this method.

Design, Formulation and Evaluation of Piroxicam Capsules Prepared by Solid Dispersion Technique.

Objective: To improve the dissolution of poorly soluble Piroxicam (PRXM) by solid dispersion technique using water soluble carriers with or without the addition of sodium lauryl sulphate (SLS) as surfactant. Methods and Materials: Solid dispersions of Piroxicam were prepared using different polymers such as polyethylene glycol (PEG 4000 and PEG 6000) polyvinylpyrrolidone (PVP K30 and PVP K90) without or with addition of 2% of (SLS). Solid dispersions were formulated in drug polymer ratios 1:1, 1:2, and 1:4, each ratio without or with 2% SLS using solvent evaporation method. The prepared formulae were assayed for drug content, production yield and stability properties. Dissolution profiles were done in phosphate buffer pH 7.4 and the in vitro release was evaluated according to the % released after 20, 30, 45 and 60 minutes. An accelerated stability study was done over 3 months at 40o and 60ºC and with relative humidity (RH) 75%. Results and Discussion: All of the formulated solid dispersions displayed better dissolution profiles as compared to the pure drug. Formulae containing 2% SLS displayed better in vitro release results compared to formulae prepared without SLS. The degradation of PRXM was slow, indicating the chemical stability of PRXM in all prepared formulae. Conclusion: A formula containing PRXM to PEG 4000 in the ratio 1:1 with 2% SLS was ranked first and gave the best results among prepared formulae.