Enhancement of Rosuvastatin Calcium Bioavailability Applying Nanocrystal Technology and in-vitro, in-vivo evaluations.
Abstract
Objective: The objective of this study is to prepare efficient dosage form using nanocrystal technology and to compare with micro and marketed
formulations for its in-vitro and the in-vivo behavior. The nanocrystal technology has good potential to enhance the dissolution profile of poorly
soluble drugs by reducing particle size, increasing surface area, and also by raising the saturation solubility of the drug.
Methods: In this study, solubility of rosuvastatin calcium is increased by adopting nanocrystal technology. Rosuvastatin calcium nanocrystals was
formulated using various stabilizers like sodium lauryl sulfate, hydroxyl propyl cellulose, hydroxyl propyl methyl cellulose, poloxamer 188, tween 80,
poly vinyl pyrrolidine, by adopting two different methods top down and bottom up techniques. Formulations were compressed and physical parameters
of tablets evaluated dissolution studies were performed to evaluate release and pharmacokinetic studies were done to evaluate in-vivo behavior.
Results: Particle size obtained by employing top down method was found to be <749.04 nm (F-1 to F-7) whereas particle size obtained by following
bottom up method was higher than 2000 nm. The micronized particles possessed a size range of 61.51 μm, whereas nanoparticle formulations showed
particle size of 0.509 μm, 0.399 μm respectively. Differential scanning calorimetry studies showed good compatibility between drug and excipients.
Friability values ranging from 0.15±0.0565% to 0.59±0.0283% and disintegration time lies between 29±1.414 and 44±1.414 seconds for the prepared
formulations. The hardness of prepared tablets was between 3.0 and 4.5±0.707 kg/cm2 which are sufficient for maintaining the integrity of tablets.
Friability, disintegration time and hardness for the micronized formulation (M-1) were 0.875±0.0919%, 50±2.828 seconds, 3.5±0.707 kg/cm2,
which are higher than the values obtained for lyophilized nanocrystals in formulation. In-vitro studies have shown a 36% increase in dissolution of
nanocrystal formulation while in-vivo studies exhibited 1.87-fold increases in the bioavailability of rosuvastatin when compared to the micronized
dosage form.
Conclusion: Formulations containing different constituents were prepared by following bottom up and top down techniques and evaluated in-vitro,
in-vivo, observed significant differences between the formulations. The results proved that the bioavailability of rosuvastatin calcium has been
improved considerably by applying nanocrystal technology. In-vitro and in-vivo evaluations showed that solubility and bioavailability have been
enhanced considerably.
Keywords: Rosuvastatin calcium, Nanocrystal technology, Solubility, Bioavailability, Pharmacokinetics.
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