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.

Assessment of hupu gum for its carrier property in the design and evaluation of solid mixtures of poorly water soluble drug - rofecoxib.

There are no reports about the pharmaceutical applications of hupu gum (HG). Hence the present study was undertaken to test its suitability in the dissolution enhancement of poorly water soluble drug. Rofecoxib (RFB) was taken as model drug. For comparison solid mixtures were prepared with carriers such as poly vinyl pyrrolidone (PVP), sodium starch glycollate (SSG) and guar gum (GG). Physical mixing (PM), co-grinding (CG), kneading (KT) and solvent evaporation (SE) techniques were used to prepare the solid mixtures, using all the carriers in different carrier and drug ratios. The solid mixtures were characterized by powder X-ray diffraction (XRD) and Fourier-transformed infrared spectroscopy (FTIR). There was a significant improvement in the dissolution rate of solid mixtures of HG, when compared with the solid mixtures of other carriers. There was an increase in dissolution rate with increase in concentration of HG upto 1:1 ratio of carrier and drug. No drug-carrier interaction was found by FTIR studies. XRD studies indicated reduction in crystallinity of the drug with increase in HG concentration. Hence HG could be a useful carrier for the dissolution enhancement of poorly water soluble drugs.

Nanosuspensions as a versatile carrier based drug delivery system--an overview.

Nanotechnology is being explored in many ways to design a new chemical entity (NCE) to an active pharmaceutical ingredient (API). Of the different nanotechnologies, Nanosuspensions has gained a lot of interest due to its ease of production and applicability to a large number of drugs. This present review article on nanosuspensions is focused on the various principles, production techniques, stability problems, various marketed formulations and current trends associated with the nanosuspensions.

Formulation, characterization and ex vivo studies of terbinafine HCl liposomes for cutaneous delivery.

BACKGROUND: The goal of effective treatment for dermal fungal infections could be highly beneficial by the delivery of antifungal drugs on skin from liposomal application. Topical delivery involves minimizing the flux of the drug through the skin while maximizing its retention on the skin. The aim of the present work was the investigation of the effects of lipids and cholesterol for the development of liposomal formulations as potential carriers for antifungal agent terbinafine HCl. Phospholipon 90H (hydrogenated phosphatidylcholine) and dimyristoylglycero-3-phosphocholine (DMPC) along with cholesterol were used for preparation of liposomes by ethanol injection method and characterized for drug content, entrapment efficiency, size, zetapotential, vesicle morphology, stability, FTIR, in vitro and ex vivo drug retention studies. RESULTS: Drug entrapment ranged between 39.46±0.91% to 70.39±0.71%. Vesicles showed good morphological characters with a narrow size distribution, in the size range of 206.9 to 344.8 nm. Gum karaya gel loaded with liposomal dispersion showed prolonged drug retention on the rat skin during ex vivo studies compared to liposomal dispersion and gum karaya plain gel loaded with drug. CONCLUSION: The prolonged retention of drug by the gum karaya gel loaded with liposomal dispersion could effectively exhibit the antifungal activity for prolonged periods for cutaneous delivery.

Bioavailability and pharmacokinetic studies of rofecoxib solid dispersion.

The present investigation deals with the determination of bioavailability of Rofecoxib solid dispersion compared to pure rofecoxib (RFB). The study of a non-blinded, open-label, crossover design was conducted in six healthy volunteers. Blood samples were collected for 12 h at specified intervals of time after the administration of formulations and analysed by suitable HPLC method. The pharmacokinetic parameters such as maximum plasma concentration (Cmax), time to reach (tmax), elimination rate constant (Kel) biological half-life (t1/2), absorption rate constant (Ka) and area under curve (AUC0-12 and AUC0-) were determined. Significant difference in the bioavailability of pure rofecoxib and solid mixture of rofecoxib prepared using hupu gum as carrier has been reported from the studies. The Peak plasma concentrations (Cmax) of 8.34 ng/mL at tmax of 4 h and Cmax of 76.84 ng/mL at tmax of 3 h were observed for RFB and solid mixture respectively. The results clearly indicated an enhancement in the bioavailability of rofecoxib in solid mixture preparation.

Development and characterization of self-nanoemulsifying drug delivery systems (SNEDDS) of atorvastatin calcium.

The main aim of the present investigation is to develop and characterize the self-nanoemulsifying drug delivery systems (SNEDDS) of atorvastatin calcium (ATV) for improving the dissolution thereby oral bioavailability and to minimize the gastric degradation. Naturally occurring different vegetable oils, various surfactants and co-surfactants were studied for ATV solubility to identify the components of SNEDDS. Ternary phase diagrams comprising surfactant, cosurfactant and oil were plotted. In the ternary phase diagrams the area of self-nanoemulsifying region was marked for the compositions that are giving dispersion with a globule size ≤ 200 nm. Effect of drug loading on the phase behavior of selected system was studied. A series of SNEDDS were prepared by selecting from the nanoemulsifying area of 2.5% ATV system. Prepared SNEDDS were evaluated for visual observations, turbidity, effect of pH of the dispersion media on globule size and zeta potential, robustness to dilution and in vitro dissolution study and optimized. FT-IR and DSC were studied for interaction between drug and excipients if any. Forced degradation and accelerated stability studies were conducted for optimized SNEDDS. ATVF 04 and 11 were selected as optimized SNEDDS due to their smaller mean globule size (75.2 and 85.8 nm respectively), lower turbidity values, faster drug release and higher DE values among the other SNEDDS. The optimized ATV SNEDDS were not affected by the pH of dissolution medium. FT-IR study revealed no interaction between drug and excipients used. Forced degradation studies indicated the stability of ATV in the gastric environment. Accelerated stability studies showed no significant changes in the mean globule size, zeta potential, drug content and drug release before and after storage of optimized SNEDDS.

Chronotherapeutic drug delivery systems: an approach to circadian rhythms diseases.

The purpose of writing this review on chronotherapeutic drug delivery systems (ChrDDs) is to review the literatures with special focus on ChrDDs and the various dosage forms, techniques that are used to target the circadian rhythms (CR) of various diseases. Many functions of the human body vary considerably in a day. ChrDDs refers to a treatment method in which in vivo drug availability is timed to match circadian rhythms of disease in order to optimize therapeutic outcomes and minimize side effects. Several techniques have been developed but not many dosage forms for all the diseases are available in the market. ChrDDs are gaining importance in the field of pharmaceutical technology as these systems reduce dosing frequency, toxicity and deliver the drug that matches the CR of that particular disease when the symptoms are maximum to worse. Finally, the ultimate benefit goes to the patient due the compliance and convenience of the dosage form. Some diseases that follow circadian rhythms include cardiovascular diseases, asthma, arthritis, ulcers, diabetes etc. ChrDDs in the market were also discussed and the current technologies used to formulate were also stated. These technologies include Contin® , Chronotopic®, Pulsincaps®, Ceform®, Timerx®, Oros®, Codas®, Diffucaps®, Egalet®, Tablet in capsule device, Core-in-cup tablet technology. A coated drug-core tablet matrix, A bi-layered tablet, Multiparticulate-based chronotherapeutic drug delivery systems, Chronoset and Controlled release microchips.

Nimesulide-modified gum karaya solid mixtures: preparation, characterization, and formulation development.

Solid mixtures of nimesulide (NS) and modified gum karaya (MGK) were prepared to improve the dissolution rate of NS. The effect of drug-carrier ratio on dissolution rate of NS was investigated by preparing the solid mixtures of different ratios by cogrinding method. Solid mixtures were also prepared by physical mixing, kneading, and solid dispersion techniques to study the influence of method of preparation. Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and equilibrium solubility studies were performed to explain the results of in vitro dissolution rate studies. It was clearly evident from the results that the NS dissolution rate was dependent on the concentration of MGK in the solid mixtures, and optimum weight ratio was found to be 1:4 (NS:MGK). Though the dissolution rate of NS from all solid mixtures prepared by different methods improved significantly, maximum improvement in dissolution rate was observed with solid dispersions. The order of methods basing on their effect on dissolution efficiency is solid dispersion > kneading > cogrinding > physical mixing > pure NS. Tablets of pure drug and solid mixtures (1:4 w/w, NS:MGK) were prepared. Though the best results from the dissolution test were obtained for the tablets containing solid dispersions, tablets containing cogrinding mixture were found to be suitable, from a practical point of view, for commercialization.

Studies on the applicability of tamarind kernel powder as a carrier in the dissolution enhancement of poorly water soluble drug, celecoxib.

In the present investigation, tamarind kernel powder (TP) was evaluated for its suitability as a carrier to improve the dissolution rate of poorly water-soluble drug, celecoxib (CC). The influence of polysaccharide concentration and method of preparation of solid mixtures on dissolution rate was investigated. Solid mixtures of CC and TP were prepared in different ratios (1:1, 1:4 & 1:9 w/w, CC:TP) using co-grinding technique to test the effect of polysac-charide concentration. Four different methods namely (i) physical mixing method (ii) co-grinding method (iii) kneading method and (iv) solvent deposition method were used to assess the effect of method of preparation. Solid mixtures were characterized by Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD) studies and solubility studies. Dissolution rate of CC was increased as the TP concentration increased and optimum weight ratio was found to be 1:4 (CC:TP). It was found that method of preparation of solid mixtures significantly effected the dissolution rate of CC from solid mixtures. The order of products basing on dissolution efficency is solvent deposition > co-grinding > kneading > physical mixing > pure CC. Among all the methods, though the solvent deposition technique improved the dissolution rate to maximum, co-grinding technique was found to be suitable from practical point of view and commercialization.

Studies on rifampicin release from ethylcellulose coated nonpareil beads.

The rifampicin release studies from ethylcellulose coated nonpareil beads were studied. Propylene glycol and Castor oil were used as plasticizers. The in vitro dissolution studies revealed that the release rate is inversely proportional to percent of coating thickness. The release rate also depends on the type of plasticizer used in the coating polymer. The mechanism of drug release follows Higuchi diffusion model. Water vapour permeation studies indicated that the water vapour transport rate through free films is directly related to the drug release rate. DSC thermograms and IR spectras revealed that there is no interaction between rifampicin and other additives. SEM photographs of coated beads, before dissolution and after dissolution, also indicates that the drug release mechanism follows diffusion model.