title: Acyclovir-Polyethylene Glycol 6000 Binary Dispersions: Mechanistic Insights.
abstract: The dissolution and subsequent oral bioavailability of acyclovir (ACY) is limited by its poor aqueous solubility. An attempt has been made in this work to provide mechanistic insights into the solubility enhancement and dissolution of ACY by using the water-soluble carrier polyethylene glycol 6000 (PEG6000). Solid dispersions with varying ratios of the drug (ACY) and carrier (PEG6000) were prepared and evaluated by phase solubility, in vitro release studies, kinetic analysis, in situ perfusion, and in vitro permeation studies. Solid state characterization was done by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) analysis, and surface morphology was assessed by polarizing microscopic image analysis, scanning electron microscopy, atomic force microscopy, and nuclear magnetic resonance analysis. Thermodynamic parameters indicated the solubilization effect of the carrier. The aqueous solubility and dissolution of ACY was found to be higher in all samples. The findings of XRD, DSC, FTIR and NMR analysis confirmed the formation of solid solution, crystallinity reduction, and the absence of interaction between the drug and carrier. SEM and AFM analysis reports ratified the particle size reduction and change in the surface morphology in samples. The permeation coefficient and amount of ACY diffused were higher in samples in comparison to pure ACY. Stability was found to be higher in dispersions. The results suggest that the study findings provided clear mechanical insights into the solubility and dissolution enhancement of ACY in PEG6000, and such findings could lay the platform for resolving the poor aqueous solubility issues in formulation development.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, AIMST University, Semeling, 08100, Bedong, Kedah Darul Aman, Malaysia. venkateskumar@aimst.edu.my.
authors.forename: Krishnamoorthy
authors.initials: K
authors.lastname: Venkateskumar
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, AIMST University, Semeling, 08100, Bedong, Kedah DarulAman, Malaysia.
authors.forename: Subramani
authors.initials: S
authors.lastname: Parasuraman
authors.affiliation: School of Distance Learning, Universiti Sains Malaysia (USM), Pulau, Penang, Malaysia.
authors.forename: Raju
authors.initials: R
authors.lastname: Gunasunderi
authors.affiliation: KMCH College of Pharmacy, Kovai Estate, Kalapatty Road, Coimbatore, Tamil Nadu, India.
authors.forename: Krishnan
authors.initials: K
authors.lastname: Sureshkumar
authors.affiliation: Spectroscopy Analytical Test Facility, Indian Institute of Science, Bengaluru, Karnataka, India.
authors.forename: M Muralidhar
authors.initials: MM
authors.lastname: Nayak
authors.affiliation: Faculty of Pharmacy, Universiti Teknologi Mara (UiTM), Puncak Alam Campus, Selangor, Dahrul Ehsan, Malaysia.
authors.forename: Syed Adnan Ali
authors.initials: SAA
authors.lastname: Shah
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, AIMST University, Semeling, 08100, Bedong, Kedah Darul Aman, Malaysia.
authors.forename: Khassen
authors.initials: K
authors.lastname: Khoo
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, AIMST University, Semeling, 08100, Bedong, Kedah Darul Aman, Malaysia.
authors.forename: Heng Wei
authors.initials: HW
authors.lastname: Kai
mesh_terms: D000212:Acyclovir / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008297:Male; D008855:Microscopy, Electron, Scanning / Q000379:methods; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000998:Antiviral Agents; D004337:Drug Carriers; C000595215:Polyethylene Glycol 6000; D011092:Polyethylene Glycols; D000212:Acyclovir
keywords: acyclovir; crystallinity; drug-polymer miscibility; solid dispersions