Nasir Abbas

Development of an ANN optimized mucoadhesive buccal tablet containing flurbiprofen and lidocaine for dental pain

Abstract A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach.

Development of Paracetamol-Caffeine co-crystals to improve compressional, formulation and in-vivo performance

Abstract Paracetamol, a frequently used antipyretic and analgesic drug, has poor compression moldability owing to its low plasticity. In this study, new co-crystals of paracetamol (PCM) with caffeine (as a co-former) were prepared and delineated. Co-crystals exhibited improved compaction and mechanical behavior. A screening study was performed by utilizing a number of methods namely dry grinding, liquid assisted grinding (LAG), solvent evaporation (SE), and anti-solvent addition using various weight ratios of starting materials. LAG and SE were found successful in the screening study. Powders at 1:1 and 2:1 weight ratio of PCM/CAF by LAG and SE, respectively, resulted in the formation of co-crystals. Samples were characterized by PXRD, DSC, and ATR-FTIR techniques. Compressional properties of PCM and developed co-crystals were analyzed by in-die heckle model. Mean yield pressure (Py), an inverse measure of plasticity, obtained from the heckle plots decreased significantly (p < .05) for co-crystals than pure drug. Intrinsic dissolution profile of co-crystals showed up to 2.84-fold faster dissolution than PCM and physical mixtures in phosphate buffer pH 6.8 at 37 °C. In addition, co-crystals formulated into tablets by direct compression method showed better mechanical properties like hardness and tensile strength. In vitro dissolution studies on tablets also showed enhanced dissolution profiles (∼90–97%) in comparison to the tablets of PCM prepared by direct compression (∼55%) and wet granulation (∼85%) methods. In a single dose sheep model study, co-crystals showed up to twofold increase in AUC and Cmax. A significant (p < .05) decrease in clearance as compared to pure drug was also recorded. In conclusion, new co-crystals of PCM were successfully prepared with improved tabletability in vitro and in vivo profile. Enhancement in AUC and Cmax of PCM by co-crystallization might suggest the dose reduction and avoidance of side effects.

An Evaluation of the Binding Strength of Okra Gum and the Drug Release Characteristics of Tablets Prepared from It

The aim of this study is to evaluate the adhesion ability of okra gum, which is gaining popularity as a tablet binder. For this purpose, gum was extracted from okra pods, and the binding strength of different concentrations (1%, 3%, and 5%) was determined quantitatively. Additionally, naproxen sodium tablets were prepared by using okra gum as a binder and were evaluated for their properties including hardness, friability, disintegration time, and dissolution rate. The binding strength values were compared with that of pre-gelatinized starch, a commonly used tablet binder. The results from universal testing machine indicate that the binding strengths of all dispersions of okra increase as the concentration increases from 1% to 5% and ranges from 2.5 to 4.5 N, which are almost twice a high as those of pre-gelatinized starch. The tablets prepared with okra gum have shown good mechanical strength with hardness values of 7–8.5 kg/cm2 and a friability <1%, comparable to tablets prepared with starch. The disintegration time was longer (7.50 min with okra gum and 5.05 min with starch paste), and the drug release from these tablets was slower than the formulations with starch. The higher binding ability of okra gum probably linked with its chemical composition as it mainly contains galactose, rhamnose, and galacturonic acid. This study concludes that okra gum is a better binder than pre-gelatinized starch, it might be explored in future for introduction as a cost-effective binder in the pharmaceutical industry.

Accessing mefenamic acid form II through high-pressure recrystallization

High-pressure crystallisation has been successfully used as an alternative technique to prepare Form II of a non-steroidal anti-inflammatory drug, mefenamic acid (MA). A single crystal of Form II, denoted as high-pressure Form II, was grown at 0.3 GPa from an ethanolic solution by using a diamond anvil cell. A comparison of the crystal structures shows that the efficient packing of molecules in Form II was enabled by the structural flexibility of MA molecules. Compression studies performed on a single crystal of Form I resulted in a 14% decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which was confirmed by the results of crystallisation at high pressure.

Formulation and evaluation of fluconazole loaded nanospongies for improved topical drug delivery

Fluconazole (an antifungal drug) loaded nanosponges (NS) were prepared by an emulsion solvent diffusion method using ethyl cellulose as the polymer. Prepared formulations were evaluated for various physicochemical parameters and in-vitro drug release. NS of fluconazole were discrete, free flowing nanosized particles with perforated orange peel-like morphology as shown by SEM analysis. A topical hydrogel formulation based on the drug loaded NS showed a prolonged release profile for the drug. Kinetic modelling on release data showed that the best fitted model was Higuchi model and release mechanism was by Fickian diffusion. FTIR and PXRD results confirmed the absence of any drug polymer interaction and stability of drug in the delivery system.

Effect of cellulose acetate phthalate and polyethylene glycol on physical properties and release of theophylline from microcapsules

O presente estudo descreve o desenvolvimento de microcapsulas de teofilina pelo metodo sem adicao de solvente e o efeito da adicao de plastificante na microencapsulacao. A liberacao foi estudada em agua destilada e os dados foram analisados por varios modelos matematicos para determinacao do mecanismo de liberacao. As microcapsulas preparadas mostraram-se esfericas, livres de corrente e com mais de 80% de farmaco encapsulado. O polimero - ftalato de acetato de celulose e o plastificante - polietileno glicol - afetaram as propriedades das microcapsulas, incluindo a liberacao do farmaco (tempo para liberacao de 50% do farmaco, T50). A formulacao com a maior proporcao de polimero e sem plastificante (F3) se mostrou como a de liberacao mais lenta, com T50 = 4,3 h, enquanto as formulacoes com menor proporcao de polimero e 20% de plastificante (m/m) (F13 &14) apresentaram a liberacao mais rapida do farmaco, com T50 de 1,2 h e 1,3 h, respectivamente. A liberacao do farmaco para a maioria das formulacoes seguiu o modelo de Higuchi. Concluiu-se, dos resultados do presente estudo, que o ftalato do acetato de celulose afeta significativamente a liberacao controlada do farmaco em agua, enquanto que a adicao de polietileno glicol aumenta ligeiramente a liberacao do farmaco.