Exploring the potential of neem and tamarind gum as release retardants: Design and statistical optimisation of vildagliptin extended release matrix systems using D-optimal quadratic mixture design.

Exploring the significant role of natural polymers in developing drug delivery systems has been a promising area of research interest. The current investigation uses a D-optimal quadratic mixture design to design and evaluate neem and tamarind gum-based vildagliptin extended-release matrix tablets. Studying the combination effect of gums is one of the major objectives. Initial screening studies were performed to select the factors and their levels. The variables selected at different levels in mg/tablet are neem gum, tamarind gum, polyvinylpyrrolidone, and lactose monohydrate. Based on the screening experiments with both gums, the polymer content of 165 mg was chosen as the highest level in the DOE. Nineteen runs were generated to screen the desired parameters as responses. The total weight of the formulation was kept constant at 275 mg. Time (hours) required for 50 %, 90 % and 100 % of drug release and tablet hardness were selected as the responses for each run. The wet granulation method was adopted, and the critical variables were optimised using the design of experiments following Design Expert software. Statistical analysis was conducted, and the optimised formulations were prepared and evaluated to compare with the predicted responses. Stability studies were performed for the optimised batches. Results indicated that the prepared batches met the compendial limits and confirmed the application of neem and tamarind gum in the development of extended-release tablets of vildagliptin for 24 h. An optimised formulation comprising of 16.52 mg of neem gum and 148.48 mg of tamarind gum with a hardness of 7.5-8.5 kp produced 50 %, 90 % and 100 % drug release in 12, 22 and 25 h.

Design by optimization and comparative evaluation of vesicular gels of etodolac for transdermal delivery.

Aim of the present study was to design vesicular gels of etodolac loaded liposomes and ethosomes for effective transdermal delivery. The physicochemical properties of vesicular gels were compared with 45% v/v ethanolic etodolac solution and commercial product (PROXYM®). The liposomes were prepared by film hydration technique whereas ethosomes were prepared by cold method respectively. Both the systems were characterized for various physicochemical properties. The size range of liposomes shows 186 nm-363 nm whereas for ethosomes 170 nm-261 nm respectively. The zeta potential of optimized liposomes and ethosomes was found to be -36.5 mV and -48.3 mV, respectively. The highest %EE of liposomes and ethosomes shows 71.5% and 78.5%, respectively. The permeation of liposomes shows in the range of 67.50%-86.06% whereas ethosomes shows 52.30%-99.49%, respectively. The optimization was done by 32 experimental design. The optimized vesicular dispersions were subjected to gel preparation using carbopol 940 NF. The prepared liposomal gel (ETO-LG) and ethosomal gel (ETO-EG) were optimized and characterized. The vesicular gels showed desirable results compared to other test formulations.

Formulation and Characterization of Pyrazinamide Polymeric Nanoparticles for Pulmonary Tuberculosis: Efficiency for Alveolar Macrophage Targeting.

Pyrazinamide, a highly specific agent against Mycobacterium tuberculosis is used as first-line drug to treat tuberculosis. The current work aims to formulate polymeric nanoparticles based drug delivery system to sustain the release profile and reduce the dosing frequency of pyrazinamide. Further aim was to target the macrophages within body fluid. These polymeric nanoparticles were prepared by simultaneous double-emulsion (W/O/W) solvent evaporation/diffusion technique. The prepared dispersions were characterized for various biopharmaceutical parameters such as particle size, zeta potential, polydispersity index, drug loading capacity, entrapment efficiency and targeting to alveolar macrophages. The formulated polymeric nanoparticles were in the particle size range of 45.51 to 300.4 nm with a maximum drug entrapment efficiency of 80.9%. The stability study of optimized batch conducted at 40±2°/75±5% relative humidity showed no significant changes up to 90 days. X-Ray Diffraction spectrum exhibits the transformation of crystalline form of drug to amorphous in the formulation. Scanning Electron Microscope image showed nanoparticles spherical in shape with smooth surface. In vitro release profiles were biphasic in nature with burst release followed by controlled release over a period of 24 h obeying diffusion mechanism. In vivo and ex vivo studies results of the study show significant uptake of the nanoparticles by alveolar macrophages through fluorescent micrograph. Polymeric nanoparticles formulation of pyrazinamide could encompass significant uptake by alveolar macrophages, the high first-pass metabolism, sustain the release of drug leading to reduction in dose, toxicity and improvement of patient compliance.

Preliminary study on antifertility activity of Enicostemma axillare leaves and Urena lobata root used in Indian traditional folk medicine.

OBJECTIVE: To evaluate the possible antifertility activity of Enicostemma axillare (E. axillare) leaves and Urena lobata (U. lobata) root in adult male Wistar albino rats. METHODS: Six groups of rats were treated with ethanolic (70%v/v) extracts of E. axillare (375 and 750 mg/kg body weight) and U. lobata root (300 and 600 mg/kg body weight) once daily for 55 days. Control groups received the distilled water and vehicle. All the treated rats had corresponding recovery groups. At the end of each treatment periods, animals were killed and organ weights, sperm characteristics, testicular and epididymal biochemicals as well as testicular enzymes were assessed. RESULTS: The E. axillare and U. lobata at tested doses did not decrease body weight, whereas the weight of testes, epididymides and seminal vesicles were significantly (P<0.01) reduced. Significantly (P<0.01) more reductions in the sperm motility, viability and counts, epididymal and testicular protein contents were noted in the rats treated with higher dose of both the plants. Both the plants at the higher dose caused a marked increase (P<0.01) in sperm morphological abnormalities, testicular cholesterol and ascorbic acid contents were remarkably increased (P<0.01), while, the activities of testicular glucose-6-phosphate dehydrogenase (G-6-PDH) and Δ(5)-3ß-hydroxy steroid dehydrogenase (Δ(5)-3ß-HSD) were significantly reduced (P<0.01). However, reversal of these changes occurred after 55 days of treatment withdrawal. CONCLUSIONS: This study suggests that the E. axillare leaves and U. lobata root reversibly inhibited spermatogenesis and steroidogenesis indicating reversible antifertility activity which could partially support the traditional of these plants as male contraceptives.

Reversible antispermatogenic and antisteroidogenic activities of Feronia limonia fruit pulp in adult male rats.

OBJECTIVE: To explore the antispermatogenic and testicular antisteroidogenic activities of Feronia limonia fruit pulp southern India. METHODS: Fourty Wistar male albino rats (Rattus norvegicus) were equally divided into four groups. Experimental groups were administered with the ethanolic extract of Feronia limonia (F. limoni) fruit pulp at doses of 250 and 500 mg/kg body weight once daily for 55 days. All treated rats had corresponding recovery groups. At the end of each treatment periods, various spermatological indices, tissue biochemicals and testicular enzymes levels were analysed. Blood profiles were also estimated. RESULTS: Compared with the control, the F. limonia fruit pulp at both dose levels did not decrease body weight, which were associated with decline in epididymal sperm count, motility, viability and increased percent of abnormal sperm. Further, F. limonia fruit pulp at 500 mg/kg body weight markedly reduced the epididymal and testicular protein content by 24.58% and 29.86%, respectively, as well as the glucose-6-phosphate dehydrogenase and Δ(5)-3ß-hydroxy steroid dehydrogenase) levels by 42.82% and 38.08%, respectively, while a significant elevation was observed in testicular cholesterol and ascorbic acid content. A gradual recovery of all parameters was observed after 55 days of treatment withdrawal. No significant alterations in haematological indices were observed. CONCLUSIONS: The present findings indicate that F. limonia fruit pulp may have reversible antispermatogenic and antisteroidogenic properties, and could partially support the traditional use as male contraceptive.

Reverse-phase, high performance liquid chromatographic method for the determination of tolterodine tartrate in routine quality control samples.

A selective, sensitive, and rugged reverse phase-high performance liquid chromatographic method has been developed for the determination of tolterodine tartrate in routine quality control samples. The mobile phase consisted of acetonitrile:phosphate buffer (pH 7.0) in 55:45 v/v ratio. The mobile phase was also used for the extraction of tolterodine tartrate from its formulations. The chromatography was carried out on a Luna 100A, C-18 (5-micro, 250 x 4.60 mm) column. The software used in the chromatographic analysis was Empower Photodiode Array (PDA) software (Waters, Milford, CT). The UV spectrophotometric determination was done at 210 nm. Retention time was found to be about 7.0 +/- 0.5 min. The standard curve was linear (r2 = 0.9997) over the concentration range of 0.1-0.3 mg/mL. The method was found to be accurate, precise, specific, and rugged. The limit of detection was 0.16 microg/mL and the limit of quantification was 0.489 microg/mL. With a short chromatographic run time, the proposed method can be used for the estimation of large number of quality control samples in a short period.

Key formulation variables in tableting of coated pellets.

Multiple unit controlled release dosage forms offer various advantages over their single unit counterparts. Most of these advantages are associated with the uniform distribution of multiparticulates throughout the gastrointestinal tract. Though coated pellets can be filled into hard gelatin capsules, tablet formulation is the preferred one because of various advantages associated with it. However, compression of coated pellets is a challenging task necessitating the optimization of various formulation and process variables. The key formulation variables include composition, porosity, size, shape and density of the pellets; type and amount of polymer coating; nature, size and amount of tableting excipients. The pellet core should be strong with some degree of plasticity. It should be highly porous, small, with an irregular shape. The critical density to achieve prolonged release was reported to lie between 2.4 and 2.8 g/cm(3). Acrylic polymer films are more flexible and more suitable for the coating of pellets to be compressed into tablets. Thicker coatings offer better resistance to frictional forces. Solvent based coatings are more flexible and have a higher degree of mechanical stability than the aqueous based ones. The tableting excipients should have cushioning property. They should not be significantly different in size and density from those of the pellet cores in order to avoid segregation. Addition of 30%-60% of tableting excipients is necessary to avoid any damage to the polymer coat and to retain its functional property.

Preparation and characterization of quercetin and rutin cyclodextrin inclusion complexes.

The objective of the present study is to prepare and characterize cyclodextrin inclusion complexes of quercetin and rutin to improve their aqueous solubility and dissolution properties. Inclusion complexes of quercetin and rutin with beta-cyclodextrin (beta-CD) and hydroxyl propyl-beta-cyclodextrin (HP-beta-CD) were prepared by kneading and coevaporation methods. Characterization of inclusion complexes was done by phase solubility analysis and was supported by X-ray powder diffractometry (XRD), differential scanning calorimetry (DSC), and Fourier-transform infra red spectroscopy (FT-IR) analysis. Inclusion complexes exhibited higher rates of dissolution than the corresponding physical mixtures and pure drug. Higher dissolution rates were observed with HP-beta-CD kneaded complexes in comparison to the products with beta-CD.