Evaluation of the effect of carrier material on modification of release characteristics of poor water soluble drug from liquisolid compacts.

Liquisolid compact is a novel dosage form in which a liquid medication (liquid drug, drug solution/dispersion in non-volatile solvent/solvent system) is converted to a dry, free flowing powder and compressed. Objective of the study was to elucidate the effect of carrier material on release characteristics of clopidogrel from liquisolid compacts. Different formulations of liquisolid compacts were developed using microcrystalline cellulose, starch maize, polyvinyl pyrollidone and hydroxypropyl methylcellulose as carrier material in three concentrations (40, 30 and 20%, w/w). Liquid vehicle was selected on the basis of solubility of clopidogrel. Colloidal silicondioxide was used as coating material and ratio of carrier to coating material was kept 10. A control formulation comprised of microcrystalline cellulose (diluents), tabletose-80 (diluents), primojel (disintegrant) and magnesium stearate (lubricant) was prepared by direct compression technique and was used for comparison. All the formulations were evaluated at pre and post compression level. Acid solubility profile showed higher solubility in HCl buffer pH2 (296.89±3.49 µg/mL). Mixture of propylene glycol and water (2:1, v/v) was selected as liquid vehicle. Drug content was in the range of 99-101% of the claimed quantity. All the formulations showed better mechanical strength and their friability was within the official limits (<1%). Microcrystalline cellulose and starch maize resulted in faster drug release while polyvinyl pyrollidone and HPMC resulted in sustaining drug release by gel formation. It is concluded from results that both fast release and sustained release of clopidogrel can be achieved by proper selection of carrier material.

Formulation development and in-vitro evaluation of gastroretentive drug delivery system of loxoprofen sodium: A natural excipients based approach.

The limitations of conventional type delivery systems to retain drug (s) in the stomach has resulted in the development of novel gastroretentive drug delivery system. We developed single-layer effervescent floating tablets of loxoprofen sodium for prolong delivery in the stomach using natural polymers xanthan gum, guar gum and semisynthetic polymer HPMCK4M. All the formulations (F1-F9) were developed by varying concentrations of xanthan gum and HPMCK4M while guar gum concentration was kept constant. Two gas generating agent (s) incorporated were sodium bicarbonate and citric acid. All compendial pre and post-compression tests results were in the acceptable limits. FTIR analysis confirmed drug-polymer compatibility. The in-vitro drug release in simulated conditions i.e., 0.1 N HCl for 12 h revealed orderly increase in total floating time, i.e., less than 6 h for F1 over 12 h for F9. Formulations F1 to F4 were not capable to retard drug release up to 12 h, whereas F5-F7 for 12 h, while F8 and F9 for more than 12 h. Data fitting in various kinetic models showed that drug release best fit in first order kinetic model and F9 in zero order. Based on results data, F7 was the best among all.

Development and Evaluation of Drug Loaded Regenerated Bacterial Cellulose-Based Matrices as a Potential Dosage Form.

Bacterial cellulose (BC) is a highly pure form of cellulose and possesses superior physico-mechanical properties with wide range of applications. These properties of BC can further be improved by various modifications, including its regeneration from the BC solution. In the current research work, regenerated BC (R-BC) matrices were prepared using N-methyl-morpholine-oxide (NMMO; 50% w/w solution in water) and loaded with model drugs, i.e., famotidine or tizanidine. The characterization of drug loaded regenerated BC (R-BC-drug) matrices was carried out using Fourier transform infrared spectroscopy (FTIR), x-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) and thermogravimetric analysis (TGA), which revealed the stability of matrices and successful drug loading. Results of dissolution studies showed immediate (i.e., >90%) drug release in 30 min. The drugs release data was found to best fit into first order kinetics model having R 2 values >0.99 for all the formulations. These results indicated that regenerated BC-based matrices had the ability to be used for delivery of orally administered drugs.

Bacterial Cellulose-Based Metallic Green Nanocomposites for Biomedical and Pharmaceutical Applications.

BACKGROUND: Bacterial cellulose (BC) is a microbial biosynthesized polymer having exceptional physical and mechanical features as compared to plants derived cellulose. BC has a wide range of applications such as traditional dessert as well as gelling, stabilizing and thickening agent in many foods. The more unconventional applications of BC include but not limited to enzymes immobilization, tissue engineering, artificial blood vessels and heart valve prosthesis, bone and cartilage regeneration, corneal replacement, skin tissues repair and dental root canal treatment. OBJECTIVE: This review presents the applications of BC expanded by preparing its nanocomposites with drugs, fibres, metals and metallic oxides. These nanocomposites have been studied for applications in drug delivery and biosensors. METHODS: The current review focuses on the potential applications of BC-based green metallic and metal-based inorganic nanocomposites as wound dressing material, a tool for microbial control, cardiovascular stenting, and as bone tissue engineering material. In addition, the potential pharmaceutical applications of BC-based green metallic nanocomposites have also been discussed. RESULTS: The reported BC-based nanocomposites owe advantages in terms of stability, environment friendliness and cost-effectiveness, prolonged therapeutic effects and biocompatibility with body tissues, with faster wound healing and negligible cytotoxicity. CONCLUSION: The current review provides a deep insight into the assessment of such nanocomposites in terms of useful applications and potential commercialization for pharmaceutical as well biomedical purposes.

Functionalized Bacterial Cellulose Microparticles for Drug Delivery in Biomedical Applications.

BACKGROUND: Bacterial cellulose (BC) has recently attained greater interest in various research fields, including drug delivery for biomedical applications. BC has been studied in the field of drug delivery, such as tablet coating, controlled release systems and prodrug design. OBJECTIVE: In the current work, we tested the feasibility of BC as a drug carrier in microparticulate form for potential pharmaceutical and biomedical applications. METHODS: For this purpose, drug-loaded BC microparticles were prepared by simple grinding and injection moulding method through regeneration. Model drugs, i.e., cloxacillin (CLX) and cefuroxime (CEF) sodium salts were loaded in these microparticles to assess their drug loading and release properties. The prepared microparticles were evaluated in terms of particle shapes, drug loading efficiency, physical state of the loaded drug, drug release behaviour and antibacterial properties. RESULTS: The BC microparticles were converted to partially amorphous state after regeneration. Moreover, the loaded drug was transformed into the amorphous state. The results of scanning electron microscopy (SEM) showed that microparticles had almost spherical shape with a size of ca. 350-400 µm. The microparticles treated with higher drug concentration (3%) exhibited higher drug loading. Keeping drug concertation constant, i.e., 1%, the regenerated BC (RBC) microparticles showed higher drug loading (i.e., 37.57±0.22% for CEF and 33.36±3.03% for CLX) as compared to as-synthesized BC (ABC) microparticles (i.e., 9.46±1.30% for CEF and 9.84±1.26% for CLX). All formulations showed immediate drug release, wherein more than 85% drug was released in the initial 30 min. Moreover, such microparticles exhibited good antibacterial activity with larger zones of inhibition for drug loaded RBC microparticles as compared to corresponding ABC microparticles. CONCLUSION: Drug loaded BC microparticles with immediate release behaviour and antibacterial activity were fabricated. Such functionalized microparticles may find potential biomedical and pharmaceutical applications.

Understanding impact of pre-dissolved polymers on dissolution behavior of soluble carbamazepine cocrystal.

Cocrystallization is a novel approach for tackling the lower solubility concerns when they can yield solution concentration a lot better than their corresponding parent drug in crystalline form. To get the actual solubility and dissolution gains offered by the cocrystals, phase changes in solution (dissolution) has to be interrupted. In current study, we selected commonly used polymers in order to study their effects on the super saturation of carbamezepine-succinic acid (CBZ-SUC) cocrystal during dissolution studies. To observe solid phase changes during dissolution in situ Raman spectroscopy was used. At the completion of each test the solid phase was analyzed by Fourier-transform infrared spectroscopy (FTIR) and powder X-Ray diffractometry. In polymers absence, no dissolution improvement was achieved by the cocrystal owing to its quick transformation to the stable carbamazepine dihydrate (CBZDH). Pre-dissolved PVP at 2% w/v concentration did not inhibit CBZ crystallization as a dihydrate, whereas at 0.025% w/v pre-dissolved hydroxypropyl methyl cellulose acetate succinate (HPMCAS) did stabilize the cocrystal in buffer solution (pH 6.8) for the course of time studied. This cocrystal stabilization resulted in enhanced CBZ solubility ( Ì´ 4fold) caused by cocrystal super saturation state. Seeding of this stable supersaturated state with 1% w/v CBZDH resulted in CBZ crystallization as dihydrate with ultimate loss of solubility advantage.

Surface modification and evaluation of bacterial cellulose for drug delivery.

The current study was designed to prepare surface modified BC matrices loaded with model drugs selected on the basis of their aqueous solubility, i.e., poorly water soluble famotidine and highly water soluble tizanidine. Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA) confirmed the successful drug loading and thermal stability of the BC matrices. In-vitro dissolution studies using USP type-II dissolution apparatus showed that most of the drug was released in 0.5-3h from famotidine loaded matrices and in 0.25-0.5h from tizanidine loaded matrices. The chemical structure, concentration of the loaded drug, concentration of the surface modifier, and pre- and post-drug loading modifications altered the physicochemical properties of BC matrices, which in turn affected the drug release behavior. In general, surface modification of the BC matrices enhanced the drug release retardant properties in pre-modification drug loading. Surface modification was found to be effective for controlling the drug release properties of BC. Therefore, these modified BC matrices have the potential for applications in modified drug delivery systems.