FORMULATION AND OPTIMIZATION OF QUERCETIN LOADED NANOSPONGES TOPICAL GEL: EX VIVO, PHARMACODYNAMIC AND PHARMACOKINETIC STUDIES

Objective: Quercetin is therapeutically hampered because of its poor solubility. The present investigation was aimed to prepare quercetin loaded nanosponges topical gel to enhance the solubility and efficacy of the drug. Methods: Quercetin nanosponges were prepared by emulsion solvent diffusion method. Developed nanosponges optimized by particle size, SEM, entrapment efficiency, FT-IR, DSC, P-XRD, In vitro studies. The optimized formulation of nanosponges was loaded into a topical gel and it was characterized by ex-vivo, in vivo Pharmacodynamic and kinetic studies. Results: The particle size and zeta potential of optimized nanosponges were found to be 188.3 nm and-0.1mV. Surface morphology was studied using SEM Analysis which showed tiny sponge-like structure and entrapment efficiency was found to be 96.5 %. In vitro drug release of optimized nanosponges was found to be 98.6% for 7hours. Optimized nanosponges entrapped gel was prepared by using carbopol 934 and hydroxypropyl methylcellulose as gelling agents. The prepared nanogels were homogenous and ex-vivo skin permeation studies of the optimized nanosponges gel was found to be 98.1% for 5 h, quercetin loaded nanosponges has shown higher skin permeation efficiency (18.4µg/cm2±2.1) compared to pure quercetin gel. The pharmacokinetic and pharmacodynamic studies showed that the quercetin loaded nanosponges has shown more effective when compared to marketed formulation. Conclusion: Quercetin loaded nanosponges gel has shown a significant increase in activity (p<0.05) compared to the marketed formulation (Voveran Emulgel)

A REVIEW ON LIQUID CRYSTALLINE NANOPARTICLES (CUBOSOMES): EMERGING NANOPARTICULATE DRUG CARRIER

Cubosomes are novel biocompatible drug delivery system and have honeycombed (cavernous) structures whose diameter size range from 10–500 nm. They appear like dots, which are likely to be spherical structures. Each dot corresponds to the presence of a pore containing aqueous cubic phase in the lipid water system. Cubosomes posse’s great significance in the field of cosmeceuticals and Pharmaceuticals due to its unique features and become an attractive choice of vehicle for in vivo drug delivery due to their low cost, safety, efficacy and versatility for controlled release application and functionalization. Cubosomes have a very simple method of preparation; biodegradability of selected lipids has the capability to encapsulate hydrophobic and hydrophilic substances. Cubosomes are considered to be versatile systems, and prepared cubosomes can be administrated by different ways such as oral, percutaneous and parenteral routes. On the whole, cubosomes offer high consequence in nano-based drug preparations for melanoma (skin cancer) treatment, targeted drug delivery systems and comprise a wide range of applications in many areas and are characterized by various parameters. Consequently, cubosomes are in progress forward of awareness in the Pharmaceutical division. This review article mainly focuses on the methods of preparation, advantages, and applications of cubosomes

CHRONOTHERAPEUTIC DELIVERY OF DICLOFENACSODIUM USING ALMOND GUM AS CARRIER FOR THE TREATEMENT OF RHEUMATOID ARTHRITIS

  Objective: The objective of the present work was to develop and evaluate a matrix system for chronotherapeutic delivery of diclofenac sodium using almond gum as a carrier for the treatment rheumatoid arthritis.Methods: Matrix tablets of diclofenac sodium were prepared using 30, 40, 50, 60, and 70% w/w of tablet using almond gum as a carrier by wet granulation technique. These tablets were compression coated with Eudragit S100 to prevent drug release in the stomach. All formulations were evaluated for hardness, friability, weight variation, drug content, in vitro and in vivo studies. The release kinetics were studied. The almond gum was characterized by viscosity measurements and Fourier transform infrared spectroscopy (FTIR) analysis. The coated (FC1 to FC5) and uncoated tablets (F1 to F5) were evaluated for in vitro release of diclofenac sodium after sequential exposure to pH 1.2, pH 7.4, and pH 6.8, respectively, for 2 hr, 3 hr, and 19 hr in the absence as well as presence of rat cecal content. The selected formulation was subjected to in vivo targeting efficacy studies by roentgenography technique.Results: In vitro release studies indicated that the matrix tablets (F1 to F5) failed to control the drug release in the physiological environment of the stomach and small intestine. On the other hand, compression-coated formulations were able to protect the tablet cores from premature drug release. In the presence of rat cecal contents, FC5 formulation has shown highest release for longer period when compared to that of FC5 in the absence of cecal contents. The values of the correlation coefficient indicated that the drug release followed zero order drug release kinetics with Peppas drug release mechanism. FTIR studies confirmed that there was no interaction between the drug and the carrier. X-ray studies confirmed that the tablet successfully reached colon without getting disintegrated in upper gastrointestinal tract.Conclusion: Based on the results, selective delivery of diclofenac sodium to the colon could be achieved using 70% w/w (FC5) of almond gum matrix tablets compression coated with Eudragit S100 as a carrier.Keywords: Diclofenac sodium, Gum almond, Eudragit S100, Roentgenography, Rat cecal content

PREPARATION AND EVALUATION OF PULSATILE DRUG DELIVERY OF FLUVASTATIN SODIUM

ABSTRACTIn the present study, an attempt was made to develop the pulsatile drug delivery of fluvastatin sodium to the colon. Formaldehyde-treated capsulebodies were used for the preparation of pulsincaps. It was sealed with a unhardened cap of the capsule. The microspheres were prepared by emulsionsolvent evaporation technique. Optimized microsphere formulations were selected based on dissolution studies. Hydrogel plug (HP) (Karaya gum andlactose in 1:1 ratio) having 4.5 kg/cm hardness and 100 mg weight was placed in the capsule opening and found that it was satisfactory to retard thedrug release in small intestinal fluid and to eject out the plugin colonic fluid and releasing the microspheres into colonic fluid after a lag time criterionof 5 hrs. The sealed capsules were completely coated by dip coating method with 5% cellulose acetate phthalate to prevent variable gastric emptying.Dissolution studies of pulsatile capsule device in media with different pH (1.2, 7.4 and 6.8) showed that drug release in the colon could be modulatedby optimizing the concentration of polymers in the microspheres. Drug-polymer interaction studies indicated no interaction in between the drug andthe polymer. Among all the formulations, fluvastatin sodium microspheres prepared with Eudragit RS 100 in 1:3 ratio shown prolonged release for aperiod of 12 hrs. The obtained results showed the capability of the system in delaying drug release for a programmable period of time and to deliverthe drug in the early morning hours when cholesterol synthesis are more prevalent.2Keywords: Fluvastatin sodium, Pulsatile, Hydrogel plug

NOVEL NANOPARTICLES FOR THE ORAL DELIVERY OF LOW MOLECULAR WEIGHT HEPARIN: IN VITRO AND IN VIVO ASSESSMENT

Objective: The objective of the present study was to prepare and evaluate a novel oral formulation of nanoparticles for the systemic delivery of low molecular weight heparin (LMWH). Methods: Nanoparticles were prepared by polyelectrolyte complexation (PEC) method using polymers sodium alginate and chitosan. Entrapment efficiency of LMWH in nanoparticles was found to be  ̴88%. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X‑ray diffraction (XRD), Scanning electron microscopy (SEM)  studies carried for nanoparticles. In vitro release studies were performed for the formulations. Ex vivo permeation studies were performed optimized formulation by using small intestine of rat and in vivo studies were conducted on rat model.Results: In vitro release studies demonstrated that the release of LMWH was negligible in the stomach and high in the small intestine. FTIR has indicated that there is no interaction between the ingredients in nanoparticle. DSC and XRD studies confirmed that the amino groups of chitosan interacted with the carboxylic groups of alginate. Invitro % drug release of 95% was shown by formulation AC5. Ex vivo permeation studies have elucidated that ̴ 73% of LMWH was transported across the epithelium. Nanoparticles have shown enhanced oral bioavailability of LMWH as revealed by 4.5 fold increase in AUC of plasma drug concentration time curve.Conclusion: The results suggest that the nanoparticles prepared can result in targeted delivery of LMWH into systemic circulation via intestinal and colon routes. Novel nanoparticles thus prepared in this study can be considered as a promising delivery system.Keywords: Antifactor Xa activity, Chitosan, Differential scanning calorimetry, Sodium alginate, Low-molecular-weight heparin, Oral bioavailability

Enhancement of solubility and oral bioavailability of poorly soluble drug Valsartan by novel solid self emulsifying drug delivery system

The main objective of present work was to prepare a solid SEDDS for enhancement of oral bioavailability of Valsartan, poorly water soluble drug. The solubility of the drug was determined in various vehicles. A pseudo ternary phase diagram was constructed to identify the self-micro emulsification region. Further, the resultant formulations were investigated for clarity, phase separation, globule size, effect of pH and dilutions and freeze-thaw stability. The optimized SMEDDS (F4) formulation of Valsartan contained Capmul MCM (Oil), Kolliphor HS 15 (Surfactant) and PEG 400 (Co-surfactant). This optimized formulation was converted in to solid SEDDS by adding required quantity of Neusilin US2 as adsorbing agent used for in vitro dissolution and bioavailability assessment. The oral bioavailability of Valsartan from solid SEDDS was 1.6-fold higher compared to that of Valsartan suspension in rats, suggesting a significant increase (p < 0.05) in oral bioavailability of Valsartan from solid SEDDS

Enhancement of solubility and oral bioavailability of poorly soluble drug Valsartan by novel solid self emulsifying drug delivery system

The main objective of present work was to prepare a solid SEDDS for enhancement of oral bioavailability of Valsartan, poorly water soluble drug. The solubility of the drug was determined in various vehicles. A pseudo ternary phase diagram was constructed to identify the self-micro emulsification region. Further, the resultant formulations were investigated for clarity, phase separation, globule size, effect of pH and dilutions and freeze-thaw stability. The optimized SMEDDS (F4) formulation of Valsartan contained Capmul MCM (Oil), Kolliphor HS 15 (Surfactant) and PEG 400 (Co-surfactant). This optimized formulation was converted in to solid SEDDS by adding required quantity of Neusilin US2 as adsorbing agent used for in vitro dissolution and bioavailability assessment. The oral bioavailability of Valsartan from solid SEDDS was 1.6-fold higher compared to that of Valsartan suspension in rats, suggesting a significant increase (p < 0.05) in oral bioavailability of Valsartan from solid SEDDS

CHITOSAN NANOPARTICLES - AN EMERGING TREND IN NANOTECHNOLOGY

The application of nanotechnology for the treatment, diagnosis, monitoring, and control of biological systems has recently been determined by the National of Health (NIH) as nanomedicine. The strategy of Nanoparticle delivery plays a significant impact on global Pharmaceutical planning and marketing. Polymeric nanoparticles are used to control the drug release, to improve the dissolution of poorly soluble drugs in addition to improve the bioavailability of degradable substances such as protein. They also enhance the uptake of hydrophilic substances across the epithelial layers and have the potential for intracellular drug delivery. The submicron size range of nanoparticles is not only suitable for parenteral application but also applicable for mucosal routes of administration, i.e., oral, nasal, and ocular mucosa which are non-invasive route. Thus nanoparticle formulations are more advantageous over traditional dosage forms. The main aim of the present review deals with the nanoparticles of chitosan, which is a natural and bio-degradable polymer. The review focuses on the isolation, purification, characteristic features, derivatives of chitosan, preparation techniques, evaluation methods and applications of chitosan nanoparticles

CHITOSAN NANOPARTICLES - AN EMERGING TREND IN NANOTECHNOLOGY

The application of nanotechnology for the treatment, diagnosis, monitoring, and control of biological systems has recently been determined by the National of Health (NIH) as nanomedicine. The strategy of Nanoparticle delivery plays a significant impact on global Pharmaceutical planning and marketing. Polymeric nanoparticles are used to control the drug release, to improve the dissolution of poorly soluble drugs in addition to improve the bioavailability of degradable substances such as protein. They also enhance the uptake of hydrophilic substances across the epithelial layers and have the potential for intracellular drug delivery. The submicron size range of nanoparticles is not only suitable for parenteral application but also applicable for mucosal routes of administration, i.e., oral, nasal, and ocular mucosa which are non-invasive route. Thus nanoparticle formulations are more advantageous over traditional dosage forms. The main aim of the present review deals with the nanoparticles of chitosan, which is a natural and bio-degradable polymer. The review focuses on the isolation, purification, characteristic features, derivatives of chitosan, preparation techniques, evaluation methods and applications of chitosan nanoparticles

FORMULATION AND IN VITRO EVALUATION OF EZETIMIBE RAPIDMELTS

Objective: The main objective of the present research was formulation and evaluation of ezetimibe rapidmelts. Methods: As ezetimibe comes under Class II drug, solubility of the drug should be increased before formulation. For that solid dispersions were prepared with β-CD and PVP K-30 using coevaporation and kneading method. Among those solid dispersions prepared with β-CD (1:1.5) using coevaporation method has given better drug entrapment values compared to other solid dispersions. Those solid dispersions were formulated as rapidmelts using direct compression. In direct compression method, rapidmelts were prepared using superdisintegrants such as crospovidone, croscarmellose sodium, and starch 1500. Those are evaluated for both pre-compression and post-compression parameters. Rapidmelts of ezetimibe were prepared using sublimation method with subliming agents camphor, urea, and ammonium bicarbonate. The concentrations of subliming agents were found to be 2.5, 5.0, and 7.5%. Results: Rapidmelts prepared using direct compression and sublimation methods were evaluated for weight variation, hardness, friability, % drug content, and disintegration time. The best formulation was subjected to stability testing for 6 months at 25°C/60% RH and 40°C/75% RH. All the prepared formulations compiled with the pharmacopeial limits. In all the formulations, results suggest that E12 formulation has given the best results. Conclusion: From the result, it was concluded that rapidmelts prepared using sublimation method which has given better result than direct compression method. That final formulation was further evaluated for in vivo studies using rabbits