Monica RP Rao
@aissmscop.com
Associate Professor, Pharmacy
AISSMS College of Pharmacy
27 years experience in teaching at AISSMS College of Pharmacy, 83 publications, 2 book chapters in Springer, 6 months industry experience in Hoechst Pharmaceuticals
EDUCATION
M Pharm (Pharmaceutics), PhD
RESEARCH, TEACHING, or OTHER INTERESTS
Pharmacology, Toxicology and Pharmaceutics, Pharmaceutical Science, General Pharmacology, Toxicology and Pharmaceutics, Materials Science
FUTURE PROJECTS
Phytoconstituents based drug delivery systems
Applications Invited
Scopus Publications
Scopus Publications
Monica RP Rao, Pranjali Gaikwad, Poonam Misal, and Santosh V. Gandhi
Elsevier BV
Monica Raghavendra Prasad Rao and Saloni A Sakharwade
EManuscript Technologies
Monica RP Rao, Sushant Deshpande, and Padmanabh Deshpande
Springer Science and Business Media LLC
Mixed polymeric micelles are potential nanocarriers for topical drug delivery. Dapsone (DAP) is an antibacterial used as anti-acne agent, but challenged by low water solubility and poor skin permeability. In the present study, DAP-loaded mixed micellar gel was developed comprising Pluronics F-68 and F-127. Micelles were prepared by solvent evaporation method and particle size, ex vivo permeation, drug loading, and entrapment efficiency were determined. Central Composite Design was used to optimize formulation. Independent variables were concentration of Pluronics at three levels while micelle size and drug loading capacities were dependent variables. Droplet size ranged from 400 to 500 nm. Transmission electron microscopy revealed spherical morphology of micelles. Optimized micelles were incorporated into gel base using HPMC K100M, Sodium CMC, and Carbopol 980 as gelling agents. Gels were evaluated for pH, drug content, spreadability, rheology, syneresis, ex vivo permeation, and subacute dermal toxicity. Compared with solubility of free DAP (0.24+0.056 µg/ml), solubility in mixed micelles was 18.42±3.4 µg/ml in water at room temperature. Order of spreadability of gels was Na CMC < HPMC < Carbopol 980. Carbopol gels displayed thixotropy with index of 3.17. Syneresis for all gels from day 0 to day 30 was found to be in range of 4.2 to 15.6% w/w. Subacute dermal toxicity studies showed no signs of erythema and edema on rat skin until 21 days. These results suggest that mixed micelles can significantly increase solubility and permeability and sustain release of DAP and are suitable carriers for topical DAP delivery in anti-acne therapies. Graphical Abstract
Monica Raghavendra Prasad Rao, Ashwini Sanjay Sonawane, Sharwari Alhad Sapate, Chetan Hasmukh Mehta, and UshaYogendra Nayak
Elsevier BV
Monica R. P. Rao, Isha Ghadge, Saurav Kulkarni, and Ashwini R. Madgulkar
Springer Nature Switzerland
Monica Raghavendra Prasad Rao, Isha Sangram Ghadge, Saurav Prasanna Kulkarni, and Tanya Asthana
Bentham Science Publishers Ltd.
Abstract: The last two years from 2020 to 2022 have seen the world face an unparalleled crisis in the form of the corona virus, which has challenged mankind as never before. The struggle and race to find a cure for the disease kept medical professionals, pharmacists, and scientists on their toes. Drug discovery by de novo approach was not an option due to its obvious downside of the enormous time required for the process. Hitherto unknown in public parlance, repurposing existing drugs showed the way forward for scientists. Drug repurposing involves redefining medical use for drugs that have crossed the drug discovery process and were approved, discontinued, or shelved. Drug repurposing or repositioning has shown effective results in treating several diseases. This review traces the journey of some repurposed drugs and provides an overview of computational methods used for repurposing, which include signature mapping, molecular docking, and in silico approaches. The review also highlights repurposed drugs for cancer, one of the most dreaded diseases, and how repurposing can prove to be a boon for many types of cancers. Concerted efforts to study this modality of drug discovery are the need of the hour. The article discusses various drugs which have been successfully repurposed for the treatment of a plethora of diseases. Drug repurposing is a silver lining that can reduce the arduous journey of discovering a definitive cure for a disease and has the potential to change the landscape of the drug discovery process.
Monica R. P. Rao, Sharwari Sapate, and Ashwini Sonawane
Springer Science and Business Media LLC
Sediment delivery model (SeDeM) system is innovative tool to correlate micromeritic properties of powders with compressibility. It involves computation of indices which facilitate direct compressibility of solids and enable corrective measures through particle engineering. Study had multiple objectives, viz, (i) to enhance solubility of BCS class II, nevirapine using solid dispersions; (ii) SeDeM analyses of excipients and solid dispersions to analyze direct compressibility; and (iii) prepare orodispersible tablets (ODT). Solid dispersions were prepared by solvent evaporation. Superdisintegrants and solid dispersions were analyzed for primary indices of dimension, compressibility, flowability, stability, and disgregability derived from micromeritic properties. Radar diagrams were constructed to provide visual clues to deficient properties for direct compressibility. ODTs were prepared using excipients which passed criteria for direct compressibility and evaluated for tablet properties. Solid dispersions with Eudragit S100 revealed 6 to 10 fold increase in solubility in various dissolution media including biorelevant media in comparison with plain drug. Solubility was found to be pH dependent. SeDeM analyses facilitated identification of superdisintegrants and excipients with unfavorable compressibility. Radar diagrams provided a clear pictorial evidence of lacunae in powder properties. Based on SeDeM results, tablets were formulated by direct compression using crosspovidone, croscarmellose sodium, and mannitol. All batches showed 40% release in first minute in simulated salivary fluid.
Monica Raghavendra Prasad Rao, Sayali Kulkarni, Ashwini Sonawane, and Sayali Sugaonkar
EManuscript Technologies
Aim: Self-nanoemulsifying Drug Delivery Systems (SNEDDS) are physically stable, isotropic mixtures of oil, surfactant and co-surfactant. The turbulence generated by peristaltic movements of the GIT causes formation of oil-in-water (o/w) nano-emulsions upon dilution. The objective of this study was to improve solubility and oral bioavailability of Cilnidipine by formulating liquid-SNEDDS. Materials and methods: Capmul PG8 NF, Cremophor RH40, and Transcutol HP were selected as oil, surfactant, and co-surfactant. Ternary phase diagrams were constructed to evaluate the nanoemulsification region. A 32 factorial design was employed to optimize L-SNEDDS with droplet size and drug release as responses. SNEDDS of CLN was evaluated for droplet size, self-emulsification time, in vitro drug release, ex-vivo permeation, pharmacokinetics and tissue distribution studies and stability studies. The optimized L-SNEDDS was converted into solid form using β-cyclodextrin nanosponges as adsorbents and evaluated in terms of micromeritics, drug content, scanning electron microscopy and powder X-ray diffraction. Results: The optimized batch exhibited droplet size of 23.70 nm, and in vitro drug release of 95.24 % in 60 min.The in-vivo studies revealed nearly 5.53 folds increase in AUC0-∞ of optimized batch of liquid SNEDDS compared to CLN which can be credited to increase in solubility and dissolution rate. Conclusion: In vivo studies revealed improved pharmacokinetic properties which were attributed to greater surface area and lymphatic absorption leading to circumvention of hepatic first pass metabolism.
Monica R. P. Rao, Rohit Vidyadhar Godbole, Sameer G. Borate, Sanskar Mahajan, and Tejal Gangwal
Informa UK Limited
Abstract Objective Improving solubility and bioavailability of albendazole (ALB). Significance ALB is a broad-spectrum anthelminthic BCS class II drug with aqueous solubility of solubility of 4.1 mg/l at 25 °C and oral bioavailability of <5%. Methods ALB nanosuspensions (NSs) were prepared by evaporative antisolvent precipitation using tocopherol polyethylene glycol succinate (TPGS) and polyvinyl pyrrolidone (PVP) as stabilizers and characterized for particle size, polydispersity index, and zeta potential. 32 factorial design was used to investigate effect of stabilizer concentration and speed of stirring on particle size. Concentration of TPGS was varied from 0.03 to 0.05% w/v and PVP K-30 was constant at 0.04% w/v. Stirring speed range was 1000–3000 rpm. Optimized NS was loaded on Espheres and coated with Eudragit S10& L100 and studied for friability, surface morphology and release kinetics. Results Factorial experiments revealed pronounced effect of TPGS on particle size. Optimized batch had particle size of 251 ± 7.2 nm and zeta potential −16.2 ± 2.68 mV. Saturation solubility showed increase of 16-fold in water whereas in phosphate buffer increase was fourfold. ALB-NS secondary coated Espheres released 94.3% drug in 10 h whereas ALB-MS (microsuspension) coated Espheres showed 58% release. A 1.3-fold increase in AUC0-10h was evident. Permeation from ALB-NS coated Espheres was 32% in 60 min while for ALB-MS coated Espheres it was 20%. Permeation increase occurred due to presence of TPGS which acts as a permeation enhancer.
Monica R. P. Rao, Kirti Bhutada, and Pauroosh Kaushal
Springer Science and Business Media LLC
Self-nanoemulsifying drug delivery systems (SNEDDS) are isotropic and thermodynamically stable mixtures of oil, surfactant, co-surfactant, and drug which emulsify spontaneously on contact with aqueous phase under mild agitation. Efavirenz used for treatment of acquired immune deficiency syndrome, is poorly water soluble and bitter tasting drug resulting in “burning mouth syndrome (BMS).” The objective of this study was to improve solubility and oral bioavailability by formulating liquid-SNEDDS and to mask bitter taste and minimize BMS. Capmul PG8 NF, Cremophor RH40, and Transcutol HP were selected as oil, surfactant, and co-surfactant. Ternary phase diagrams were constructed to evaluate the nanoemulsification region. A 32 factorial design was employed to optimize L-SNEDDS with droplet size and drug release as responses. Optimized batch was subjected to evaluation of taste by human panel method and electronic tongue, cloud point determination, phase separation, in vivo and stability studies. The optimized batch exhibited droplet size of 21.53 nm, polydispersibility index 0.155, and in vitro drug release of 92.26% in 60 min. The in vivo studies revealed 4.5 times enhancement in oral bioavailability. Taste evaluation indicated reduced the intensity and shortened duration of BMS. The formulation was stable at 40°C ± 75% RH after 3 months. Comparison between standard bitter drug and efavirenz in SNEDDS formulation using e-tongue by principal component analysis revealed significant differences in discrimination index, computed by multivariate data analysis. This study demonstrated that L-SNEDDS may be an alternative approach to improve solubility and oral bioavailability and for masking the bitterness of efavirenz.
Monica R. P. Rao and Laxmi S. Babrekar
OMICS Publishing Group
To overcome the limited solubility and low bioavailability of efavirenz a liposomal drug delivery system was formulated using thin film hydration technique. Optimal ratios of total lipid blend:drug, soya lecithin:cholesterol and polyethylene glycol 400 concentration were determined using Box Behnken design with vesicle size and entrapment efficiency as responses. The optimized liposomal dispersions were characterized by vesicle size, entrapment efficiency, transmission electron microscopy, in vitro drug release and in vivo pharmacokinetics. The vesicle size was found to be in range of 694.5-1200.0 nm and entrapment efficiency was above 80 %. Statistical studies revealed that vesicle size and entrapment efficiency increased with increase in total lipid blend:drug and polyethylene glycol 400 concentration. Transmission electron microscopy showed that unilamellar and multi-lamellar vesicles were formed. Optimized liposomal dispersion was solidified using nanosponges. Solid liposomes were characterized by micromeritics, differential scanning calorimetry, Fourier-transform infrared spectroscopy and bioavailability. As compared to plain drug a 10-fold increase in percent release was observed in 6 h in liposomal preparation. In vivo pharmacokinetic studies revealed that bioavailability increases 2 folds as compared to plain drug. Lipid-based drug delivery like liposomes are taken up through lymphatic pathway. Since the human immunodeficiency virus settles in lymphoid organs, lymphatic drug delivery can be advantageous in the treatment of acquired immune deficiency syndrome. Thus, the pharmacokinetic studies demonstrated that efavirenz-loaded liposomes could significantly upgrade the solubility and oral bioavailability of efavirenz and improve the therapeutic efficacy.
Monica R. P. Rao, Sneha P. Raut, C. T. Shirsath, Monali B. Jadhav, and Pranoti A. Chandanshive
OMICS Publishing Group
Lipid-based self-nanoemulsifying drug delivery system was explored to improve the oral bioavailability and target specificity of mebendazole for treatment of lymphatic worm infestations. Ternary phase diagrams were constructed to select suitable oil-surfactant mixture. Liquid self-nanoemulsifying drug delivery system consisting of Capmul MCM L8, Chromophore RH40 and tocopherol polyethylene glycol succinates a pre-concentrate was systematically optimized using 32 full factorial designs. β-cyclodextrin-based nanosponges were used to prepare solid self-nanoemulsifying drug delivery system. Characterization of liquid self-nanoemulsifying drug delivery system was carried out using percent transmission, globule size, zeta potential, polydispersity index and drug content. Globule size in the range of 50-90 nm and zeta potential of –5 to –12 mV was obtained, which co-related well with percent transmission. Powder X-ray diffraction, differential scanning calorimetry and scanning electron microscope of solid self-nanoemulsifying drug delivery system indicated the presence of mebendazole as a molecular dispersion. Ex vivo studies showed nearly five-fold increase in the flux. In vivo studies showed two-fold increase in bioavailability. Significant enhancement in drug dissolution and saturation solubility from solid self-nanoemulsifying drug delivery system resulted in an increase in the bioavailability. Besides this, greater surface area, improved release, P-gp modulation potential of excipients and lymphatic bypass via Peyer’s patches protected drug from hepatic first pass metabolism all of which would contribute to the observed improved bioavailability. Lymphatic transport of drug could achieve target specificity in lymphatic filariasis.
Monica R. P. Rao, Jagruti Chaudhari, Francesco Trotta, and Fabrizio Caldera
Springer Science and Business Media LLC
Rilpivrine is BCS class II drug used for treatment of HIV infection. The drug has low aqueous solubility (0.0166 mg/ml) and dissolution rate leading to low bioavailability (32%). Aim of this work was to enhance solubility and dissolution of rilpivirine using beta-cyclodextrin-based nanosponges. These nanosponges are biocompatible nanoporous particles having high loading capacity to form supramolecular inclusion and non-inclusion complexes with hydrophilic and lipophilic drugs for solubility enhancement. Beta-cyclodextrin was crosslinked with carbonyl diimidazole and pyromellitic dianhydride to prepare nanosponges. The nanosponges were loaded with rilpivirine by solvent evaporation method. Binary and ternary complexes of drug with β-CD, HP-β-CD, nanosponges, and tocopherol polyethylene glycol succinate were prepared and characterized by phase solubility, saturation solubility in different media, in vitro dissolution, and in vivo pharmacokinetics. Spectral analysis by Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry was performed. Results obtained from spectral characterization confirmed inclusion complexation. Phase solubility studies indicated stable complex formation. Saturation solubility was found to be 10–13-folds higher with ternary complexes in distilled water and 12–14-fold higher in 0.1 N HCl. Solubility enhancement was evident in biorelevant media. Molecular modeling studies revealed possible mode of entrapment of rilpivirine within β-CD cavities. A 3-fold increase in dissolution with ternary complexes was observed. Animal studies revealed nearly 2-fold increase in oral bioavailability of rilpivirine. It was inferred that electronic interactions, hydrogen bonding, and van der Waals forces are involved in the supramolecular interactions.
Monica R.P. Rao, Laxmi Babrekar, Vaishali S. Kharpude, and Jagruti Chaudhari
Elsevier BV
Monica R P Rao and Chaitanya Shirsath
Springer Science and Business Media LLC
Efavirenz is a non-nucleoside reverse transcriptase inhibitor which is chronically prescribed for HIV patients. However, it exhibits solubility-limited bioavailability. Aim of this work was to enhance the solubility and dissolution of the Biopharmaceutical Classification System (BCS) class II drug efavirenz, using beta-cyclodextrin-based nanosponges. Nanosponges have high drug loading capacity and are effective for solubility enhancement. Beta-cyclodextrin was crosslinked with carbonates in different ratios to prepare nanosponges. The nanosponges were loaded with efavirenz by solvent evaporation method and the nanosponge with higher drug loading capacity was selected for further studies. Binary and ternary complexes with EFA, NS, and PVP K30 were prepared and characterized by phase solubility, solution state interaction, saturation solubility, in vitro dissolution, and in vivo pharmacokinetics. Spectral analysis by Fourier transform infrared spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and field emission scanning electron microscopy was performed. Results obtained from spectral characterization confirmed inclusion complexation. Stability constant for ternary complex was found to be 1997 lit/mole, which indicates stable complex formation. The saturation solubility was found to be 17-fold higher with ternary complex in distilled water and about 4-fold in simulated gastric fluid. In vitro dissolution was improved 3 folds with ternary complex. Ternary nanosponge complexes were found to have 2-fold increase in oral bioavailability of efavirenz as compared to plain drug.
R. P. R Monica, H. J Shilpa, S. T Swati, and S. K Vaishali
OMICS Publishing Group
Microporous osmotic tablets were developed using controlled porosity membrane, which delivers drug in a controlled manner for prolonged period of time. The objective of the present investigation was to formulate and evaluate an oral osmotic drug delivery system for the antidepressant drug venlafaxine hydrochloride to achieve zero order release. Venlafaxine hydrochloride was selected as it has a short biological half-life and high aqueous solubility. Drug-excipient compatibility was studied using Fourier transform infrared spectroscopy. Core tablets were prepared by wet granulation method followed by coating. Sodium chloride and potassium chloride (1:1) were used as osmotic agents in the core tablet and polymers Eudragit RLPO and RSPO (1:1) were used for coating along with sorbitol (70% w/w) as pore formers. The tablets showed desired sustained release profile for 24 h. Optimization studies were performed to study the effect of concentration of osmotic agent and pore former on drug release (t50% and t90%). From in vitro release studies, it was evident that drug release was independent of dissolution media, agitation intensity, but highly dependent on the concentration of pore forming agents, osmotic agent and weight gain of the tablet coating. Scanning electron microscopy confirmed the microporous structure of optimized batch. The optimized formulation gave desired once a day release of venlafaxine hydrochloride without using laser drilling technique which would make it more patient compliant and cost effective.
Monica Rao, Deepak Kumar Agrawal, and Chaitanya Shirsath
Informa UK Limited
Abstract Parkinson’s disease is a degenerative disorder of the central nervous system (CNS). The most obvious symptoms are movement-related such as shaking, rigidity, slowness of movement and difficulty with walking, rigid muscular movements and difficulty in chewing and swallowing especially solid dosage forms. Ropinirole is an anti-Parkinson drug that has low oral bioavailability which is primarily due to first-pass metabolism. The objective of proposed work was to increase bioavailability of ropinirole and avoid patient discomfort by formulating thermoreversible in situ nasal gel. Thermoreversible nasal gels were prepared by cold method using Pluronic F-127 and hydroxy methyl propyl cellulose (HPMC K4M) as gelling agents. Formulations were evaluated for various parameters such as drug content, pH, gelling time, gelling temperature, gel strength, mucoadhesive force, ex vivo diffusion, histological studies and in vivo bioavailability. Formulations displayed gelation at nasal temperature and the gelation time was found to be less than mucociliary clearance time. The nasal residence time was seen to be increased due to mucoadhesion and increased gel strength. The nasal gel formulations showed ex vivo drug release between 56–100% in 5 h. Histological study of sheep nasal mucosa revealed that the gel had a protective effect on the mucosa unlike plain ropinirole which showed evidence of moderate cellular damage. A fivefold increase in bioavailability in brain was observed on nasal administration as compared to IV route. Thermoreversible in situ nasal gel was found to a promising drug delivery for Parkinsonian patients.
Monica R.P. Rao, Deepa U. Warrier, Snehal R. Gaikwad, and Prachi M. Shevate
Elsevier BV
MonicaR P Rao, DeepaU Warrier, and ShivaniH Rao
OMICS Publishing Group
The aim of the present study was to modify psyllium seed polysaccharide and evaluate the modified polysaccharide as release retardant in tablets employing ciprofloxacin hydrochloride as model drug. Studies on polysaccharide from psyllium husk has been reported but no work has been reported on characterization and modification of the polysaccharide present in the psyllium (Plantago ovata) seed and the use of the modified polysaccharide as a release retardant in tablets. In this study, the seed gum was modified using sodium trimetaphosphate as crosslinking agent. Sustained release matrix tablets of ciprofloxacin hydrochloride were prepared by wet granulation using various drug-polymer ratios. The polymers investigated were psyllium polysaccharide, phosphorylated psyllium polysaccharide and widely used release retardant hydroxypropyl methylcellulose K100M. The tablets were evaluated for hardness, friability, drug content, swelling profile and in vitro dissolution studies. The matrix tablets containing 1:3 proportion of drug-phosphorylated psyllium polysaccharide was found to have higher hardness as compared to tablets containing 1:1 and 1:2 proportions. The results of swelling behavior in water showed that the tablets containing 1:3 drug:phosphorylated psyllium polysaccharide ratio had swelling comparable to that of tablets containing 1:3 drug:hydroxypropyl methylcellulose ratio. The in vitro dissolution studies shows that the dissolution rate was retarded from 98.41 to 37.6% in 6 h with increase in concentration of phosphorylated psyllium polysaccharide from 100 to 300 mg. Formulations containing psyllium polysaccharide showed complete drug release in 8 h whereas those formulated with phosphorylated psyllium polysaccharide exhibited extended drug release over the 12 h period. Drug release kinetic studies revealed that drug release followed Korsmeyer-Peppas model.
Monica R. P. Rao and Rohini C. Bhingole
Informa UK Limited
Abstract Context: Gabapentin was selected to formulate oral controlled release dry suspension because of short biological half life of 5–7 h and low bioavailability (60%). Gabapentin is a bitter drug so an attempt was made to mask its taste. Objective: To formulate and evaluate controlled release dry suspension for reconstitution to increase the bioavailability and to control bitter taste of drug. Materials and methods: Cyclodextrin based nanosponges were synthesized by previously reported melt method. The nanosponge–drug complexes were characterized by FTIR, DSC and PXRD as well as evaluated for taste and saturation solubility. The complexes were coated on Espheres by a suspension layering technique followed by coating with ethyl cellulose and Eudragit RS-100. A dry powder suspension for reconstitution of the microspheres was formulated and evaluated for taste, redispersibility, in vitro dissolution, sedimentation volume, leaching and pharmacokinetics. Results and discussion: The complexes showed partial entrapment of drug nanocavities. Significant decrease in solubility (25%) was observed in the complexes than pure drug in different media. The microspheres of nanosponge complexes showed desired controlled release profile for 12 h. Insignificant drug leaching was observed in reconstituted suspension during storage for 7 days at 45 °C/75% RH. Nanosponges effectively masked the taste of Gabapentin and the coating polymers provided controlled release of the drug and enhanced taste masking. The results of in vivo studies showed increase in bioavailability of controlled release suspension by 24.09% as compared to pure drug. Conclusion: The dry powder suspension loaded with microspheres of nanosponges complexes can be proposed as a suitable controlled release drug delivery for Gabapentin.
Ashwini R. Madgulkar, Monica R. P. Rao, and Deepa Warrier
Springer International Publishing
Monica Raghavendra Prasad Rao and Swapnil Uttamrao Shelar
EManuscript Technologies
There are various approaches commonly used for gastric retention, one of which is raft forming system. Floating oral in situ gel is a type of raft forming system. The present work concerns with the formulation, evaluation and optimization of floating oral in situ gel of Itopride Hydrochloride for controlled release. Gellan gum has been used as a gel forming polymer and calcium carbonate as cross linking agent and Ca 2+ ion source, and HPMC K100M as release retardant. The floating oral in situ gel undergoes gelation by ion sensitive mechanism. In this formulation 3 2 factorial designs was performed and the effect of variation in concentration of gellan gum and HPMC K100M on drug release at 1 h, 6 h, and viscosity was evaluated. The gel was evaluated for other parameters like floating lag time, floating duration, gel strength, density, pH, in vitro drug release, drug content, and in vitro gelling capacity. The results of 3 2 full factorial design revealed that the concentration of gellan gum and of HPMC K100M significantly affected the dependent variables i.e. drug release at 1 h, at 6 h, and viscosity. A controlled release profile was observed for these formulations. The drug release mechanism was found to follow Korsmeyer-Peppas model. In vivo studies revealed higher T max of gel compared to plain drug which is suggestive of slower absorption. However the AUC 0-12 h was found to be nearly 90% higher than plain drug.
M. Rao and A. Bajaj
Georg Thieme Verlag KG
Abstract Telmisartan, an orally active nonpeptide angiotensin II receptor antagonist is a BCS Class II drug having aqueous solubility of 9.9 µg/ml and hence oral bioavailability of 40%. The present study involved preparation of nanosuspensions by evaporative antisolvent precipitation technique to improve the saturation solubility and dissolution rate of telmisartan. Various stabilizers such as TPGS, PVPK 30, PEG 6000 were investigated of which TPGS was found to provide maximum decrease in particle size and accord greater stability to the nanosuspensions. Box-Behnken design was used to investigate the effect of independent variables like stabilizer concentration, time and speed of stirring on particle size of nanosuspensions. Pharmacodynamic studies using Goldblatt technique were undertaken to evaluate the effect of nano-sizing on the hypotensive effect of the drug. Concentration of TPGS and speed of rotation were found to play an important role in particle size of the nanosuspensions whereas time of stirring displayed an exponential relationship with particle size. Freeze dried nanocrystals obtained from nanosuspension of least particle size were found to have increased saturation solubility of telmisartan in different dissolution media. The reconstituted nanosuspension was found to reduce both systolic and diastolic blood pressure without affecting pulse pressure and heart rate. Statistical tools can be used to identify key process and formulation parameters which play a significant role in controlling the particle size in nanosuspensions.
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