Varsha Pokharkar

Publications (16)37.89 Total impact

• Article: Pioglitazone solid dispersion system prepared by spray drying method: in vitro and in vivo evaluation.

  Varsha Pokharkar, Manisha Kutwal, Leenata Mandpe
  [show abstract] [hide abstract]
  ABSTRACT: Objective: Pioglitazone is a thiazolidinedion antidiabetic agent which decreases insulin resistance in the periphery and in the liver, resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Pioglitazone is insoluble in water and has a low dissolution rate. The objective of the current work was to improve aqueous solubility of pioglitazone by the solid dispersion approach using the spray drying technique. Design: In this study, various hydrophilic polymers such as PVP K17, PVP K30, and HPMC E3 were used to prepare pioglitazone solid dispersion by the spray drying method. Main outcome measures: Characterization of solid dispersion included solubility, particle size, surface area analysis, differential scanning calorimetry, infrared spectroscopy, x-ray diffraction, and dissolution test. In vivo hypoglycaemic activity was studied in Swiss albino mice. Results: Results showed that there was significant improvement in solubility and dissolution rate in solid dispersion containing PVP K17 than in that of the pure drug. This in turn resulted in improved pharmacodynamic activity, giving 2 fold mean percentage glucose inhibition as compared to the pure drug; thus the solid dispersion strategy proved to be potentially beneficial for improving the in vivo hypoglycaemic activity of pioglitazone. Conclusion: Increase in pioglitazone solubility and in vitro dissolution in solid dispersion was followed by improved in vivo hypoglycaemic activity. LAY ABSTRACT: The aim of the present study was to prepare and evaluate solid dispersion of pioglitazone by the spray drying method. Various hydrophilic polymers were used for preparation of solid dispersion. Pioglitazone is an oral antidiabetic agent effective for reactive hypoglycaemia and aggravated glycaemic metabolism associated with insulin resistance. The prepared solid dispersion was evaluated for saturation solubility, drug content, differential scanning calorimetry, x-ray diffraction, infrared spectroscopy, and stability as per International Conference on Harmonisation guidelines. The glucose-lowering response of the optimized formulation was also studied in Alloxan-induced diabetic Swiss Albino mice. The formulation containing hydrophilic polymers showed a satisfactory drug release pattern compared to the pure drug. Further, when in vivo hypoglycaemic response of pure drug, prepared solid dispersion, and marketed formulation was compared, the optimized solid dispersion batch revealed significant improvement in hypoglycaemic activity. Hence, the present study reveals that the formulation of solid dispersion of pioglitazone with hydrophilic polymer exhibits good release properties as well as in vivo antihyperglycemic activity.
  PDA journal of pharmaceutical science and technology / PDA. 01/2013; 67(1):23-34.
• Article: Porphyran capped gold nanoparticles as a novel carrier for delivery of anticancer drug: in vitro cytotoxicity study.

  Vinod Venkatpurwar, Anjali Shiras, Varsha Pokharkar
  [show abstract] [hide abstract]
  ABSTRACT: In the present study, we have explored porphyran as a reducing agent for one pot size controlled green synthesis of gold nanoparticles (AuNps) and further investigated its application as a carrier for the delivery of an anticancer drug. The prepared AuNps showed surface plasmon resonance centered at 520 nm with average particle size of 13±5 nm. FTIR spectra suggested that the sulfate moiety is mainly responsible for reduction of chloroauric acid. The capping of the AuNps with porphyran was evident from the negative zeta potential value responsible for the electrostatic stability. Thus, porphyran acts as reducing as well as capping agent. These AuNps are highly stable in a wide range of pH and electrolyte concentration. Porphyran capped AuNps exhibited enhanced cytotoxicity on human glioma cell line (LN-229) as compared to native porphyran. Consequently, these AuNps have been utilized as a carrier for delivery of the anticancer drug doxorubicin hydrochloride (DOX). Spectroscopic examination revealed that DOX conjugated onto AuNps via hydrogen bonding. The release of DOX from DOX loaded AuNps was found to be sixfold higher in acetate buffer (pH 4.5) as compared to physiological buffer (pH 7.4). Further, the DOX loaded AuNps demonstrated higher cytotoxicity on LN-229 cell line as compared with an equal dose of native DOX solution. This established the potential of these AuNps as a carrier for anticancer drug delivery.
  International journal of pharmaceutics 03/2011; 409(1-2):314-20. · 2.96 Impact Factor
• Article: Gold nanoparticles as a potential carrier for transmucosal vaccine delivery.

  Varsha Pokharkar, Devika Bhumkar, K Suresh, Y Shinde, S Gairola, S S Jadhav
  [show abstract] [hide abstract]
  ABSTRACT: The transmucosal administration of vaccines leads to development of systemic as well as local immune response. However, development of delivery systems targeted at these immunologically active sites remains a practical challenge. The objective of the present study was to explore the potential of chitosan reduced gold nanoparticles (AuNps) for the transmucosal delivery of tetanus toxoid vaccine. Two different nanoparticulate systems were developed utilizing chitosan. Tetanus toxoid was loaded on chitosan nanoparticles and chitosan reduced AuNps. The current study clearly demonstrated that subcutaneous TT administration lead to generation of systemic response, but did not elicit any mucosal response. However TT loaded AuNps were able to generate a significantly higher mucosal response following oral administration. In conclusion, a novel approach utilizing chitosan reduced gold nanoparticles for the development of transmucosal vaccine formulation was successfully demonstrated.
  Journal of Biomedical Nanotechnology 02/2011; 7(1):57-9. · 4.22 Impact Factor
• Article: Polyelectrolyte stabilized antimalarial nanosuspension using factorial design approach.

  Vividha Dhapte, Varsha Pokharkar
  [show abstract] [hide abstract]
  ABSTRACT: The use of most of the antimalarials like pyrimethamine is restricted owing to their poor solubility and low bioavailability problems. In this study the combined effects of polyelectrolyte stabilizers on effective particle size reduction and stability of antimalarial nanosuspension using a factorial design approach. Stable nanosuspension with submicron sized particles were obtained by combining non-ionic polyelectrolyte with either of the ionic polyelectrolytes tested. Factorial design was found to be a sound approach to analyze the effects of stabilizers on preparation of pyrimethamine nanosuspension.
  Journal of Biomedical Nanotechnology 02/2011; 7(1):139-41. · 4.22 Impact Factor
• Article: Biocompatible gellan gum-reduced gold nanoparticles: cellular uptake and subacute oral toxicity studies.

  Sheetal Dhar, Vishal Mali, Subhash Bodhankar, Anjali Shiras, B L V Prasad, Varsha Pokharkar
  [show abstract] [hide abstract]
  ABSTRACT: Currently gold nanoparticles are being explored for drug delivery and other biomedical applications; therefore it is necessary to study the fate of such nanoparticles inside the body. The objective of the present study was to investigate the cellular uptake and toxicity of the gold nanoparticles synthesized using a microbial polysaccharide, gellan gum, as a capping and reducing agent. The cellular uptake of gold nanoparticles was studied on mouse embryonic fibroblast cells, NIH3T3 and human glioma cell line, LN-229. The cellular uptake study indicated that the gellan gum-reduced gold nanoparticles were located in cancer cells (LN-229) while no uptake was observed in normal mouse embryonic fibroblast cells (NIH3T3). The toxicity of the gold nanoparticles was evaluated by carrying out subacute 28 day oral toxicity studies in rats. Subacute administration of gum-reduced gold nanoparticles to the rats did not show any hematological or biochemical abnormalities. The weight and normal architecture of various organs did not change compared with control. The current findings, while establishing the specific uptake of nanoparticles into cancerous cells, also demonstrates that the gellan gum-reduced gold nanoparticles are devoid of toxicity in animals following oral administration.
  Journal of Applied Toxicology 11/2010; 31(5):411-20. · 2.48 Impact Factor
• Article: Cytotoxicity of sophorolipid-gellan gum-gold nanoparticle conjugates and their doxorubicin loaded derivatives towards human glioma and human glioma stem cell lines.

  Sheetal Dhar, E Maheswara Reddy, Asmita Prabhune, Varsha Pokharkar, Anjali Shiras, B L V Prasad
  [show abstract] [hide abstract]
  ABSTRACT: Biocompatible gold nanoparticles were synthesized by using a naturally occurring gum--Gellan Gum--as a capping and reducing agent. These were further conjugated with sophorolipids which again were accessed through a biochemical transformation of a fatty acid. The cellular uptake of sophorolipid-conjugated gellan gum reduced gold nanoparticles and their cytotoxicity on human glioma cell line LN-229 and human glioma stem cell line HNGC-2 were investigated. Quite surprisingly even the simple sophorolipid-conjugated gellan gum reduced/capped gold nanoparticles showed greater efficacy in killing the glioma cell lines and, gratifyingly, the glioma stem cell lines also. The cytotoxic effects became more prominent once the anti cancer drug doxorubicin hydrochloride was also conjugated to these gold nanoparticles.
  Nanoscale 11/2010; 3(2):575-80. · 5.91 Impact Factor
• Source

  Available from: srce.hr

  Article: Ternary complexation of carvedilol, beta-cyclodextrin and citric acid for mouth-dissolving tablet formulation.

  Varsha Pokharkar, Abhishek Khanna, Vinod Venkatpurwar, Sheetal Dhar, Leenata Mandpe
  [show abstract] [hide abstract]
  ABSTRACT: The purpose of this study was to improve the solubility and dissolution rate of carvedilol by forming a ternary complex with beta-cyclodextrin and citric acid and to formulate its mouth-dissolving tablets. The rationale for preparing mouth-dissolving tablet of carvedilol was to make the drug available in a soluble form in the mouth, which would facilitate its absorption from the buccal cavity. This would help to overcome its first-pass metabolism and thereby improve bioavailability. Phase solubility studies revealed the ability of beta-cyclodextrin and citric acid to complex with carvedilol and significantly increase its solubility. Ternary complexation of carvedilol was carried out with beta-cyclodextrin and citric acid by physical mixing, kneading and spray drying methods and the prepared complexes were characterized by Fourier transform infra red spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy and complexation efficiency. The complex obtained by the spray drying method resulted in highest complexation efficiency and a 110-fold increase in the solubility of carvedilol. The mouth-dissolving tablets formulated using the spray dried complex with suitable excipients showed 100 % dissolution within five minutes. Accelerated stability studies of mouth-dissolving tablets carried out as per ICH guidelines revealed that the tablets were stable.
  Acta Pharmaceutica 07/2009; 59(2):121-32. · 0.91 Impact Factor
• Article: Acute and subacute toxicity studies of chitosan reduced gold nanoparticles: a novel carrier for therapeutic agents.

  Varsha Pokharkar, Sheetal Dhar, Devika Bhumkar, Vishal Mali, Subhash Bodhankar, B L V Prasad
  [show abstract] [hide abstract]
  ABSTRACT: The objective of the present study was to evaluate the oral toxicity of chitosan reduced gold nanoparticles so as to demonstrate its applicability for drug delivery application. Acute oral toxicity studies in female rats documented no deaths or treatment related complications. The LD50 value of gold nanoparticles was found to be greater than 2000 mg/kg. In case of sub-acute oral toxicity studies, gold nanoparticles were administered orally to male and female rats for a period of 28-days. At the end of study blood samples were collected for haematology and biochemical analysis. For histopathological analysis, organs of animals were weighed and processed for examination. All animals survived the duration of the study, with no significant changes in clinical signs, body weight, food consumption, hematological parameters, organ weights and histopathological findings. These studies establish that chitosan reduced gold nanoparticles produced no treatment related toxicity in rats following oral administration, thus can be exploited for potential therapeutic applications.
  Journal of Biomedical Nanotechnology 06/2009; 5(3):233-9. · 4.22 Impact Factor
• Article: Preparation and evaluation of miconazole nitrate-loaded solid lipid nanoparticles for topical delivery.

  Mangesh R Bhalekar, Varsha Pokharkar, Ashwini Madgulkar, Nilam Patil, Nilkanth Patil
  [show abstract] [hide abstract]
  ABSTRACT: The purpose of this study was to prepare miconazole nitrate (MN) loaded solid lipid nanoparticles (MN-SLN) effective for topical delivery of miconazole nitrate. Compritol 888 ATO as lipid, propylene glycol (PG) to increase drug solubility in lipid, tween 80, and glyceryl monostearate were used as the surfactants to stabilize SLN dispersion in the SLN preparation using hot homogenization method. SLN dispersions exhibited average size between 244 and 766 nm. All the dispersions had high entrapment efficiency ranging from 80% to 100%. The MN-SLN dispersion which showed good stability for a period of 1 month was selected. This MN-SLN was characterized for particle size, entrapment efficiency, and X-ray diffraction. The penetration of miconazole nitrate from the gel formulated using selected MN-SLN dispersion as into cadaver skins was evaluated ex-vivo using franz diffusion cell. The results of differential scanning calorimetry (DSC) showed that MN was dispersed in SLN in an amorphous state. The MN-SLN formulations could significantly increase the accumulative uptake of MN in skin over the marketed gel and showed a significantly enhanced skin targeting effect. These results indicate that the studied MN-SLN formulation with skin targeting may be a promising carrier for topical delivery of miconazole nitrate.
  AAPS PharmSciTech 02/2009; 10(1):289-96. · 1.43 Impact Factor
• Source

  Available from: Anjali Shiras

  Article: Natural gum reduced/stabilized gold nanoparticles for drug delivery formulations.

  Sheetal Dhar, E Maheswara Reddy, Anjali Shiras, Varsha Pokharkar, B L V Prasad
  [show abstract] [hide abstract]
  ABSTRACT: "Gellan Gum", widely used in food and confectionary industry as a thickening and gelling agent, has been employed as a reducing and stabilizing agent for the synthesis of gold nanoparticles. These nanoparticles display greater stability to electrolyte addition and pH changes relative to the traditional citrate and borohydride reduced nanoparticles. Subsequently these have been used to load anthracycline ring antibiotic doxorubicin hydrochloride. The drug loaded on these nanoparticles showed enhanced cytotoxic effects on human glioma cell lines LN-18 and LN-229.
  Chemistry 11/2008; 14(33):10244-50. · 5.93 Impact Factor
• Article: Studies on formulation development of mucoadhesive sustained release itraconazole tablet using response surface methodology.

  Ashwini Madgulkar, Shivajirao Kadam, Varsha Pokharkar
  [show abstract] [hide abstract]
  ABSTRACT: The purpose of this research was to prepare and evaluate sustained release mucoadhesive tablets of Itraconazole. It is practically insoluble in aqueous fluids hence its solid dispersion with Eudragit E100 was prepared by spray drying. This was formulated in matrix of hydrophilic mucoadhesive polymers Carbopol 934P (CP) and Methocel K4M (HPMC). The formulation was optimized using a 3(2) factorial design. Amounts of CP and HPMC were taken as formulation variables for optimizing response variables i.e. mucoadhesion and dissolution parameters. The optimized mucoadhesive formulation was orally administered to albino rabbits, and blood samples collected were used to determine pharmacokinetic parameters. The solid dispersion markedly enhanced the dissolution rate of itraconazole. The bioadhesive strength of formulation was found to vary linearly with increasing amount of both polymers. Formulations exhibited drug release fitting Peppas model with value of n ranging from 0.61 to 1.18. Optimum combination of polymers was arrived at which provided adequate bioadhesive strength and fairly regulated release profile. The experimental and predicted results for optimum formulations were found to be in close agreement. The formulation showed C (max) 1898 +/- 75.23 ng/ml, t (max) of the formulation was 2 h and AUC was observed to be 28604.9 ng h/ml.
  AAPS PharmSciTech 10/2008; 9(3):998-1005. · 1.43 Impact Factor
• Article: Development of trilayered mucoadhesive tablet of itraconazole with zero-order release

  Ashwini Madgulkar, Shivajirao Kadam, Varsha Pokharkar
  [show abstract] [hide abstract]
  ABSTRACT: Itraconazole is practically insoluble in water; large interindividual and intraindividual variations of its oral bioavailability are reported. A mucoadhesive drug delivery system is useful to prolong the retention time of a dosage form in the stomach, thereby improving the oral bioavailability of the drug. Solid dispersion of itraconazole with Eudragit E100 was prepared by spray-drying method to improve dissolution. Trilayered mucoadhesive tablet was prepared, with inner core containing solid dispersion of the drug and with carbopol and HPMC sandwiched between two layers of hydrophilic mucoadhesive polymer mixture of carbopol and Hydroxypropyl methyl cellulose (HPMC). Amounts of Carbopol 934P (CP) and Methocel K4M (HPMC) were varied in the outer coat around the solid dispersion. The drug-release pattern for all the formulation combinations was found to be nonfickian, approaching zero-order kinetics. Suitable combination of two polymers provided adequate bioadhesive strength and sustained-release profile with zero-order kinetics.
  Asian Journal of Pharmaceutics. 01/2008;
• Article: Gold nanoparticles as carriers for efficient transmucosal insulin delivery.

  Hrushikesh M Joshi, Devika R Bhumkar, Kalpana Joshi, Varsha Pokharkar, Murali Sastry
  [show abstract] [hide abstract]
  ABSTRACT: Nanomaterials have gained tremendous importance in biology and medicine because they can be used as carriers for delivering small molecules such as drugs, proteins, and genes. We report herein the binding of the hormone insulin to gold nanoparticles and its application in transmucosal delivery for the therapeutic treatment of diabetes mellitus. Insulin was loaded onto bare gold nanoparticles and aspartic acid-capped gold nanoparticles and delivered in diabetic Wistar rats by both oral and intranasal (transmucosal) routes. Our principle observations are that there is a significant reduction of blood glucose levels (postprandial hyperglycemia) when insulin is delivered using gold nanoparticles as carriers by the transmucosal route in diabetic rats. Furthermore, control of postprandial hyperglycemia by the intranasal delivery protocol is comparable to that achieved using the standard subcutaneous administration used for type I diabetes mellitus, thus showing considerable promise for further development.
  Langmuir 02/2006; 22(1):300-5. · 4.19 Impact Factor
• Article: Effect of penetration enhancers on gel formulation of Zidovudine: in vivo and ex vivo studies.

  Varsha Pokharkar, Sheetal Dhar, Nripendra Singh
  [show abstract] [hide abstract]
  ABSTRACT: To overcome many challenges associated with antiretroviral drug therapy, novel drug delivery systems present an opportunity for formulation scientists to improve the management of patients with HIV/AIDS. The purpose of this study was to prepare a transdermal delivery system for zidovudine using different penetration enhancers incorporated in carbopol 971P gel and to evaluate the same for rheology, percent drug content, drug deposition, in vitro, ex vivo, and in vivo permeation across rat skin. The rheology studies indicated that 1% w/w carbopol gel had a higher linear viscoelastic region, good creep recovery, and desirable viscosity. Among all gel formulations, gel containing cineole and menthol as penetration enhancers attained a steady-state flux of 5.9 mg/cm(2)/h and 5.4 mg/cm(2)/h of zidovudine, respectively, leading to plasma concentration in the therapeutic range. The drug deposition was also found to be highest in the case of gel containing cineole and menthol as penetration enhancers. The results indicated a linear relationship between in vitro flux and in vivo bioavailability of zidovudine transdermal gel.
  PDA journal of pharmaceutical science and technology / PDA. 64(4):337-47.
• Article: Studies on formulation development of mouth dissolving tablets of Carvedilol.

  Varsha Pokharkar, Sheetal Dhar, Leenata Mandpe
  [show abstract] [hide abstract]
  ABSTRACT: Carvedilol a poorly water soluble drug undergoes extensive first pass metabolism, which reduces its bioavailability to 25-30%. Mouth dissolving tablets of Carvedilol were prepared with the purpose of delivering the drug directly into the systemic circulation and bypassing the hepatic first pass metabolism with a concomitant increase in bioavailability. The solubility of Carvedilol was improved by forming inclusion complex with cyclodextrin which was then further used for the formulation of mouth dissolving tablet. Differential scanning calorimetry and Infrared spectroscopy results indicated no incompatibilities between drug-excipient mixtures. Effect of three different superdisintegrants on disintegration was studied. The formulations were evaluated for drug content, content uniformity, friability, disintegration time and in-vitro dissolution. Tablets containing Carvedilol-beta-cyclodextrin complex exhibited good tablet properties, with 90% drug dissolved within 5 min. This demonstrated the effectiveness of using various superdisintegrants and Carvedilol-beta-cyclodextrin complex in formulation of mouth dissolving tablet.
  Hindustan antibiotics bulletin 49-50(1-4):21-8.
• Article: Poly(alkylene carbonate)s by the carbonate interchange reaction of aliphatic diols with dimethyl carbonate: synthesis and characterization

  Varsha Pokharkar, S. Sivaram
  [show abstract] [hide abstract]
  ABSTRACT: Poly(alkylene carbonate)s have been synthesized by the melt-phase interchange reaction of aliphatic diols with dimethyl carbonate. Aliphatic polycarbonates with inherent viscosities of 0.3 to 0.8 dlg−1 have been obtained. Polycarbonates derived from alicyclic diols show a Tg below room temperature and a Tm in the range 50–60°C. However, the polycarbonate derived from a cyclic diol, namely 1,4-bis(hydroxymethyl)-cyclohexane, shows a Tg of + 35°C and a Tm of + 97°C, the highest yet reported for this class of polymers.
  Polymer. 36(25):4851-4854.