Investigation of Cyclodextrin-Based Nanosponges for Solubility and Bioavailability Enhancement of Rilpivirine
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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.
KEY WORDSbioavailability nanosponges beta-cyclodextrin inclusion complex rilpivirine
The authors would like to thank Dr. Ashwini Madgulkar Principal, AISSMS College of Pharmacy, Pune-01, Maharashtra (India) for providing necessary help and facilities to carry out the research work and also thankful to Mylan Laboratories, Hyderabad (India) for providing drug as gift sample.
Compliance with Ethical Standards
Approval to carry out in vivo studies was obtained from Institutional Animal Ethics Committee, AISSMS College of Pharmacy (Approval from: AISSMS/CPCSEA/IAEC/PT-01/02/2K17) and their guidelines were followed for the studies.
Conflict of Interest
The authors declare that they have no conflict of interest.
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