Mangesh Bhalekar
@emp116
Professor (Pharmacetics)
All India Shri Shivaji Memorial Society's College of Pharmacy
EDUCATION
M Pharm ( Pharmaceutics) PhD
RESEARCH, TEACHING, or OTHER INTERESTS
Pharmaceutical Science, Pharmacy
Scopus Publications
Scopus Publications
Tejinder K. Marwaha, Ashwini Madgulkar, Mangesh Bhalekar, Kalyani Asgaonkar, Rajesh Gachche, and Pallavi Shewale
Springer Science and Business Media LLC
Mangesh Bhalekar and Sachin Dubey
Elsevier
Sagar Trivedi, Shubhangi Thool, Kamlesh Wadher, Mangesh Bhalekar, and Priyanka Bire
Elsevier BV
Tejinder Kaur Marwaha, Ashwini Madgulkar, Mangesh Bhalekar, and Kalyani Asgaonkar
Wiley
Manoj Aswar, Mangesh Bhalekar, Akshata Trimukhe, and Urmila Aswar
Elsevier BV
Tejinder Kaur, Ashwini Madgulkar, Mangesh Bhalekar, and Kalyani Asgaonkar
Bentham Science Publishers Ltd.
Background: In pharmaceutical research drug discovery and development process is timeconsuming and expensive. In many cases, it produces incompetent results due to the failure of in vitro and in vivo conventional approaches. Before any new drug is placed in the market it must undergo rigorous testing to get FDA approval. Due to the several limitations imposed by the drug discovery process, in recent times in silico approaches are widely applied in this field. The purpose of this review is to highlight the current molecular docking strategies used in drug discovery and to explore various advances in the field. Methods: In this review we have compiled database after an extensive literature search on docking studies which has found its applications relevant to the field of formulation and development. The papers retrieved were further screened to appraise the quality of work. In depth strategic analysis was carried out to confirm the credibility of the findings. Results: The papers included in this review highlight the promising role of docking studies to overcome the challenges in formulation and development by emphasizing it’s applications to predict drug excipient interactions which in turn assist to increase protein stability; to determine enzyme peptide interactions which maybe further used in drug development studies; to determine the most stable drug inclusion complex; to analyze structure at molecular level that ascertain an increase in solubility, dissolution and in turn the bioavailability of the drug; to design a dosage form that amplify the drug discovery and development process. Conclusion: This review summarizes recent findings of critical role played by molecular docking in the process of drug discovery and development. The application of docking approach will assist to design a dosage form in the most cost effective and time saving manner.
Ashwini R. Madgulkar, Mangesh R. Bhalekar, and Ashwini A. Kadam
Springer Science and Business Media LLC
Lopinavir is a BCS Class IV drug exhibiting poor bioavailability due to P-gp efflux and limited permeation. The aim of this research was to formulate and characterize microspheres of lopinavir using thiolated xyloglucan (TH-MPs) as carrier to improve its oral bioavailability without co-administration of ritonavir. Thiomeric microspheres were prepared by ionotropic gelation between alginic acid and calcium ions. Interaction studies were performed using Fourier transform infrared spectroscopy (FT-IR). The thiomeric microspheres were characterized for its entrapment efficiency, T80, surface morphology, and mucoadhesion employing in vitro wash off test. The microspheres were optimized by 32 factorial design. The optimized thiomeric microsphere formulation revealed 93.12% entrapment efficiency, time for 80% drug release (T80) of 358.1 min, and 88% mucoadhesion after 1 h. The permeation of lopinavir from microspheres was enhanced 3.15 times as determined by ex vivo study using everted chick intestine and increased relative bioavailability over 3.22-fold over combination of lopinavir and ritonavir as determined by in vivo study in rat model.
Mangesh R. Bhalekar, Ashwini R. Madgulkar, Puja S. Desale, and Gyce Marium
Informa UK Limited
Abstract The purpose of this work was to formulate piperine solid lipid nanoparticle (SLN) dispersion to exploit its efficacy orally and topically. Piperine SLN were prepared by melt emulsification method and formula was optimized by the application of 32 factorial design. The nanoparticulate dispersion was evaluated for particle size, entrapment efficiency and zeta potential (ZP). Optimized batch (128.80 nm average size, 78.71% entrapment efficiency and −23.34 mV zeta potential) was characterized for differential scanning calorimetry (DSC), X-ray diffraction which revealed amorphous nature of piperine in SLN. The prepared SLN were administered orally and topically to CFA-induced arthritic rats. Ex vivo study using Franz diffusion cell indicate that piperine from SLN gel formulation accumulates in the skin. Pharmacodynamic study result indicates both the topical and oral piperine evoked a significant response compared to orally administered chloroquine suspension. The results of ELISA show significant reduction in TNFα in treated rat which might be the reason behind the DMARD action of piperine SLN.
Mangesh Bhalekar, Prashant Upadhaya, and Ashwini Madgulkar
Springer Science and Business Media LLC
Mangesh R. Bhalekar, Prashant G. Upadhaya, Ashwini R. Madgulkar, Sanjay J. Kshirsagar, Akanksha Dube, and Utkarsh S. Bartakke
Informa UK Limited
Abstract Darunavir is effective against wild-type and PI-resistant HIV, and has an oral bioavailability of 37%. It needs to be combined with ritonavir, which increases the bioavailability to 82%. The aim of this study was to evaluate the in-vivo efficacy of the darunavir-SLN and demonstrate lymphatic transport as a contributing pathway in increasing the drug bioavailability. The SLN was prepared by hot-homogenization technique using GMS as lipid. In-vitro drug release from SLN at the 12th hour was retarded (80.6%) compared to marketed tablet (92.6%). Ex-vivo apparent permeability of the freeze-dried SLN across everted rat intestine was 24 × 10−6 at 37 °C and 5.6 × 10−6 at 4 °C. The presence of endocytic process inhibitors like chlorpromazine and nystatin reduced it to 18.8 × 10−6 and 20.2 × 10−6, respectively, which established involvement of endocytic mechanism in the uptake of SLN. In-vivo pharmacokinetic studies on rats demonstrated increase in the AUC of SLN (26) as compared to that of marketed tablet (13.22), while the presence of lymphatic uptake inhibitor cycloheximide lowered the AUC of SLN to 17.19 which further led credence to the involvement of lymphatic uptake behind improved bioavailability. The detection of darunavir in the lymphatic fluid of the rats administered with darunavir-SLN further reinforced the conclusion of SLN being taken up by the lymphatic system.
Ashwini Madgulkar, Mangesh R. Bhalekar, and Amrita A. Dikpati
Elsevier BV
Mangesh R. Bhalekar, Prashant G. Upadhaya, and Ashwini R. Madgulkar
Elsevier BV
Mangesh R. Bhalekar, Rajesh V. Bargaje, Prashant G. Upadhaya, Ashwini R. Madgulkar, and Sanjay J. Kshirsagar
Elsevier BV
Sudhir T. Bansode, Sanjay J. Kshirsagar, Ashwini R. Madgulkar, Mangesh R. Bhalekar, and Mithun M. Bandivadekar
Informa UK Limited
Abstract Context: Lipoidal systems have particularly shown potential for specific accumulation in areas with inflamed tissue increasing the selectivity of local drug delivery. Objective: Formulation and evaluation of self-microemulsifying drug delivery system (SMEDDS) for colon-specific drug delivery for effective treatment of colonic diseases. Method: Ternary phase diagram was used to optimize level of oil, surfactant and co-surfactant to optimize SMEDDS and were evaluated for percent transmittance, emulsification time, in vitro release, myeloperoxidase (MPO) activity and intestinal accumulation. The spray dried SMEDDS were filled in capsules which were enteric coated with Eudragit S-100 at 10% weight gain to ensure SMEDDS delivery at colon. The spray dried SMEDDS were also evaluated for IR, DSC, XRD, SEM and stability study. Result: In ternary phase diagram, Capmul MCM C8 and Capmul PG12 NF with surfactant (Tween 20) and co-surfactant (PG) in ratio 2:1 and 3:1, respectively, showed maximum emulsification area. These liquid SMEDDS show maximum transmittance, globule size of 90–30 nm. The spray-dried SMEDDS with diluents show good flow property. The units of MPO activity show lower level as compared to pure drug and control group, histopathology results supports better healing with SMEDDS. This was attributed to accumulation of SMEDDS in inflammatory area as compared to drug which was further proved by accumulation study. Enteric-coated capsule containing SMEDDS are able to deliver drug, specifically at the colonic region. Conclusion: Higher accumulation of lipoidal drug in inflammatory area and specific release of liposomes by enteric-coated capsules provide better option for the treatment of colonic disease.
Ashwini R. Madgulkar, Mangesh R. Bhalekar, Kalyani D. Asgaonkar, and Amrita A. Dikpati
Elsevier BV
Mangesh Bhalekar, Prashant Upadhaya, and Ashwini Madgulkar
Springer Science and Business Media LLC
Mangesh R. Bhalekar, Prashant G. Upadhaya, Sandip D. Nalawade, Ashwini R. Madgulkar, and Sanjay J. Kshirsagar
Medknow
Savita Sonawane, Mangesh Bhalekar, and Shamkant Shimpi
Elsevier BV
MangeshRamesh Bhalekar, PrashantGirish Upadhaya, Satish Reddy, SanjayJ Kshirsagar, and AshwiniRaghvendra Madgulkar
BRNSS Publication Hub
M. Bhalekar, A. Madgulkar, S. Gunjal, and A. Bagal
Parenteral Drug Association, Inc.
The objective of this study was to investigate the combined influence of three independent variables in the preparation of glipizide microspheres by the spray-drying method. A three factor, three level Box-Behnken design was used to derive polynomial equations and construct response surface plots to predict responses. The independent variables selected were concentration of polymer (xyloglucan) (X1), amount of crosslinking agent (X2), and feed rate (X3). Fifteen batches were prepared and evaluated for percentage drug entrapment and time for 80% drug release (t80). Response surface plots were constructed to demonstrate the combined effects of factors X1, X2, and X3 on response percent entrapment. The optimal microsphere preparations displayed a percent entrapment between 96.96 and 98.11 and a t80 between 420 and 439 min. The microspheres had particle size between 3 and 6 microns, and differential scanning chromatography thermograms showed the presence of glipizide in amorphous form in microspheres. LAY ABSTRACT: Multiparticulate dosage forms are pharmaceutical formulations in which the active substance is present as number of small independent subunits. The microspheres as drug delivery systems are especially suitable for providing oral controlled release formulations with low risk of dose dumping, Microspheres can be blended suitably to attain different release patterns. Glipizide is recommended orally for treatment of type II diabetes and is administered in 2 or 3 doses of 2.5 to 10 mg per day. The development of controlled-release dosage form would offer effective control by releasing drug over period of time. The present work describes formulation of microspheres containing glipizide using the tamarind seed polysaccharide or xyloglucan as carrier. The spray-drying method was used to formulate the microspheres and variables (concentration of xyloglucan, amount of crosslinking agent, and feed rate) affecting performance parameters such as time for 80% drug release and percent drug entrapment were optimized using a statistical design (Box Behnken design). The microspheres had particle size between 3 and 6 microns, had entrapment between 97 and 99%, and sustained the drug release beyond 7 hours.