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Title: Design Pharmacokinetic and Pharmacodynamic Evaluation of Nanocarriers for Raloxifene Hydrochloride in the EffectiveTreatment of Post menopausal Osteoporosis
Researcher: N. ADITYA
Keywords: Pharmacokinetic and Pharmacodynamic,Evaluation of Nanocarriers,Raloxifene Hydrochloride,EffectiveTreatment
University: Birla Institute of Technology and Science
Completed Date: 
Abstract: The objective of this work was to design and evaluate different nanocarriers for oral newlinedelivery of raloxifene hydrochloride. Raloxifene hydrochloride is a selective estrogen newlinereceptor modulator (SERM) and is useful in treatment of postmenopausal osteoporosis and newlinebreast cancer. It exhibits low oral bioavailability (less than 2%) and high inter-patient newlinevariability in humans due to its poor solubility across GIT and extensive intestinal newlineglucuronidation. In order to achieve the broader objective of this work, analytical and newlinebioanalytical methods were first developed and validated for accurate and precise estimation newlineof Raloxifene in both bulk and biological samples. Extensive preformulation studies were newlinecarried out to establish physicochemical properties of Raloxifene that could further aid in newlineselection of appropriate excipients and manufacturing conditions. newlineLipid based and polymeric nanocapsules/nanoparticles were developed for delivery of newlineraloxifene. Biodegradable materials of synthetic (poly-and#949;-caprolactone) and natural origin newline(lipids, soy lecithin and chitosan) were used to produce different types of carrier systems for newlineraloxifene. All the formulations were extensively characterized and evaluated. Manufacturing newlineconditions for the formulations were optimized using design of experiments approach. In newlinesome cases, hybrid designs were used to get a better understanding of the factors affecting newlineproperties of nanocarriers like particle size, surface charge and drug entrapment efficiency. newlineOptimized formulations were subjected to extensive pharmacokinetic evaluation (after oral newlineand intravenous administration) in female Wistar rats. Further, time-dependent biodistribution newlinepatterns for both free drug and nanocarriers were obtained. Mechanistic studies in newlinepresence of various cell uptake inhibitors like chlorpromazine and nystatin were performed to newlinedecipher the mechanisms involved in the intestinal uptake of these nanocarriers. For lipid newlinexviii newlinebased nanoparticles, role of lymphatic uptake in bioavailability enhancement of raloxifene
Pagination: 10.7 MB
Appears in Departments:Pharmacy

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