Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer based controlled release tablets of aceclofenac to simultaneously enhance the solubility and bioavailability

The aim of this study was to enhance the solubility of Aceclofenac with a new polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer (Soloplus ®) and formulate it in controlled release (CR) tablet dosage form by direct compression method with HPMC K-15. Solid dispersions were prepared in different ratio of Aceclofenac and Soloplus ® as F1, F2 and F3 with different polymer ratios i.e. 30%, 50%, and 70% respectively. All the quality control tests were performed for the prepared controlled release tablets. Drug polymer interaction studies of Aceclofenac and Soloplus ® were carried using FTIR and XRD. Dissolution study was carried out against Alkaris ® as a standard reference. The formulation F3 showed optimum results and followed zero order kinetics. The Soloplus ® improved the solubility of the drug and the CR formulation enhanced the delivery in a sustained manner. Hence, the CR formulation enhanced the delivery of aceclofenac in a sustained manner, thereby an efficient drug delivery may lead to an effective anti-inflammatory activity.

Design and In vitro Evaluation of floating tablets Containing Atazanavir Sulphate.

The main of the research work to develop sustained release floating matrix tablets of ATZ, which were designed to extend the gastric residence time and prolong the drug release after oral administration. Different grades of polymers such as EC and HPMC K100M were used in order to get the desired floating and sustained release profile over prolonged period of time. All the formulations extended the drug release up to 24 hours and more and the formulations were optimized for the desired release profiles. The release and floating property was depends on the polymer type and polymer proportion. The formulation prepared with Ethyl cellulose and HPMC K100M has more floating time than the formulation prepared with the Ethyl cellulose alone. The FTIR study shows that there is no drug-polymer interaction. This study gives the preliminary idea about the development of the floating drug delivery systems of Atazanavir without the use of gas generating agent.

Formulation and Characterization of Febuxostat loaded Nanostructured Lipid Carriers (NLCs) - Gel for Topical Treatment of Gout

Background: The aim of present study was to formulate and characterize Nano Structured lipid carriers (NLCs) of Febuxostat (FB) incorporated in gel for the treatment of Gout. FB is a Xanthine Oxidase (XO) inhibitor drug used for chronic Gout and hyperuricemia. FB is BCS class II drug so water solubility is very poor and due to its poor solubility and wettability, it leads to poor dissolution. The hot high pressure homogenization technique was used in this study to improve physicochemical property of FB. Method: The carbopol 934 was used to prepare NLCs Gel of FB. The NLCs of FB was prepared in different drug: polymer ratios w/w (2:1), (1:1), (1:2), (1:3) and (1:4) with solid lipid (Stearic Acid) and liquid lipid (Oleic acid). The preformulation study of FB included FTIR study melting point, standard calibration curves and drug polymer interaction study. Result: The NLCs (1:3) showed high entrapment and drug content. The NLCs gel formulation had 87% release within 6 hours in controlled manner. Conclusion: NLCs gel modifies the drug release, increases the bioavailability and reduces side effects of FB. The prepared gel is the efficient formulation for the better treatment of chronic Gout and hyperuricemia. The research findings have shown the undesirable side effects associated with the oral route can be reduced by use of NLCs formulation through transdermal route in an effective manner.

Mucoadhesive In Situ Rectal Gel Loaded with Rifampicin: Strategy to Improve Bioavailability and Alleviate Liver Toxicity

Although it is a front-line in tuberculosis treatment, rifampicin (RF) exhibits poor oral bioavailability and hepatotoxicity. Rectal mucoadhesive and in situ rectal gels were developed to overcome drug drawbacks. A RF/polyethylene glycol 6000 co-precipitate was first prepared in different ratios. Based on the drug solubility, the selected ratio was investigated for drug/polymer interaction and then incorporated into in situ rectal gels using Pluronic F127 (15%) and Pluronic F68 (10%) as a gel base and mucoadhesive polymers (HPMC, sodium alginate and chitosan). The formulations were assessed for gelation temperature and gel strength. The selected formulation was investigated for in vivo assessments. The results showed that a 1:1 drug/polymer ratio exhibited satisfying solubility with the recorded drug/polymer interaction. Depending on their concentrations, adding mucoadhesive polymers shifted the gelation temperature to lower temperatures and improved the gel strength. The selected formulation (F4) did not exhibit any anal leakage or marked rectal irritation. Using a validated chromatographic analytical method, F4 exhibited higher drug absorption with a 3.38-fold and 1.74-fold higher bioavailability when compared to oral drug suspension and solid suppositories, respectively. Toxicity studies showed unnoticeable hepatic injury in terms of biochemical, histopathological and immunohistochemical examinations. Together, F4 showed a potential of enhanced performance and also offered lower hepatic toxicity, thus offering an encouraging therapeutic alternative.

Formulation and in vitro Evaluation of Nystatin-loaded Albumin Microparticles for the Treatment of Leishmaniosis

Background: The current treatments of leishmaniosis are far from ideal since they require the administration of toxic and poorly tolerated drugs that still fail to treat the intracellular infection. Micro-particles are very promising drug carriers for leishmaniosis treatment, considering the involved parasites’ life cycle and the pharmacokinetics of micro-particles. Objective: The aim of this study is to develop a novel formulation of Nystatin (Nys) that could be administered systemically and might be used for therapy of Leishmaniosis. Method: Nys microspheres were formulated using albumin as a carrier by spray drying for the preparation of microspheres for intravenous administration. Nys microspheres were characterized morphologically and evaluated for particle size, product yield, encapsulation efficiency and for drug-polymer interaction. AntiLeishmanial activity against Leishmania tropica was tested and the microspheres’ phagocytosis by murine macrophages was investigated. An in vitro hemolysis study was carried out for the novel formulation and for the free Nys. Results: The average size of microspheres was found to be less than 5 μm. Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) confirmed no significant interactions between albumin and Nys. The anti-leishmanial activity of Nys microspheres was higher than that for free Nys with an IC50 value of (18.1 μg/mL). Uptake study in murine macrophage confirmed the targetability of the prepared microspheres. The in vitro hemolysis study indicated reduced hemolysis and suitability of the microspheres for parenteral administration. Conclusion : Spray drying was used successfully to prepare high loaded Nys microspheres with high antileishmanial activity and less hemolysis effect.

DEVELOPMENT AND CHARACTERIZATION OF ORODISPERSIBLE TABLETS OF PROPRANOLOL HYDROCHLORIDE USING CALCIUM CROSS-LINKED CASSIA FISTULA GUM AND CROSS CARMELLOSE SODIUM

Objective: The present investigation was aimed towards developing calcium crosslinked derivative of carboxymethylated cassia fistula gum and crosscarmellose sodium based orodispersible tablets (ODTs) of propranolol hydrochloride for enhancing the bioavailability and efficacy. Methods: Orodispersible tablets (ODTs) of propranolol hydrochloride was formulated using natural (a carboxymethylated derivative of cassia fistula gum) and synthetic polymer (crosscarmellose sodium) by wet and dry granulation, lyophilization and cotton candy methods and then finally compressed by direct compression. The prepared ODTs were evaluated for several parameters such as hardness, friability, in vitro disintegration time, in vitro drug release. In vivo and stability studies were carried out on optimized formulation coding PC1. Results: Drug polymer interaction were judged by FT-IR, DSC and XRD. The optimized formulation coding PC1 prepared by cotton candy process containing 2.5% w/w of crosslinked cassia fistula gum has the least disintegration time (18.9±0.4s), weeting time (12.5±0.8s) and relased the drug of 88.2% within 10 min in contrast to croscarmellose sodium. In vivo absorption studies revealed that same formulation has Cmax (µg/ml) 2.13±0.73, tmax (h) 0.21±0.17 and (µg ml-1 h-1) 14.33±1.59. Conclusion: This research manuscript clearly shows the successful development of the ODTs loaded with an antihypertensive drug, namely propranolol hydrochloride. The formulation developed by cotton candy process utilizing crosslinked cassia fistula gum as a natural superdisintegrant in contrast to other existing techniques can be a best option over synthetic superdisintegrant i.e. crosscarmellose sodium. The prepared ODTs was enhanced the absorption rate by lowering tmax, which inturn enhance the bioavailability and the efficacy of drug.

Molecular Interactions for the Curcumin-Polymer Complex with Enhanced Anti-Inflammatory Effects

The molecular interactions between compound and polymeric carriers are expected to highly contribute to high drug load and good physical stability of solid dispersions. In this study, a series of amorphous solid dispersions (ASD) of Curcumin (Cur) were prepared with different polymers by the solvent evaporation method. With the carrier polyvinylpyrrolidone (PVP), the amorphous solid dispersion system exhibits a better solubility and stability than that with poloxamers and HP-β-CD due to the strong drug-polymer interaction. The drug/polymer interaction and their binding sites were investigated by combined experimental (XRD, DSC, FTIR, SEM, Raman, and 1H-NMR) and molecular dynamics simulation techniques. The Curcumin ASD demonstrated enhanced bioavailability by 11-fold and improved anti-inflammatory activities by the decrease in cytokine production (MMP-9, IL-1β, IL-6, VEGF, MIP-2, and TNF-α) compared to the raw Curcumin. The integration of experimental and modeling techniques is a powerful tool for the rational design of formulation development.