title: Compritol®888 ATO a lipid excipient for sustained release of highly water soluble active: formulation, scale-up and IVIVC study.
abstract: The potential of Compritol(®)888 ATO as a release modifier to retard the release of highly water soluble drug, metoprolol succinate (MPL) was exploited. Different ratios of Compritol(®)888 ATO versus MPL were utilized and the effect of various formulation methods was evaluated to sustain the release of MPL. MPL: Compritol(®)888 ATO in 1:2 ratio could successfully retard the release of MPL. Melt granulation method "as hot process" was found to be effective when compared to direct compression and wet granulation. The in vitro release characteristics of tablets were studied in pH 6.8 phosphate buffer at 50 rpm using USP Type II apparatus. Formulation F7 retarded MPL release with ~90% release after 20 h. Stability studies showed no significant difference (f2>50) in MPL release profile after three months of storage period at 25 ± 2°C/60 ± 5% RH and 40 ± 2°C/75 ± 5% RH. The bioavailability of sustained release tablets, F7 was compared with commercially available tablets, MetXL50 in 12 healthy human volunteers in a crossover design. Plasma concentration of MPL was determined using HPLC with fluorescence detector. IVIVC correlation was obtained by deconvoluting the plasma concentration-time curve using a model independent Wagner-Nelson method. Correlations of fraction of drug dissolved in vitro and fraction of drug absorbed in vivo displayed a significant linear relationship for sustained release tablets of MPL.
authors.affiliation: Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai- 400098. India.. mangal.nagarsenker@gmail.com.
authors.forename: Shilpa N
authors.initials: SN
authors.lastname: Patere
authors.forename: Neha S
authors.initials: NS
authors.lastname: Desai
authors.forename: Ankitkumar S
authors.initials: AS
authors.lastname: Jain
authors.forename: Prashant P
authors.initials: PP
authors.lastname: Kadam
authors.forename: Urmila M
authors.initials: UM
authors.lastname: Thatte
authors.forename: Nithya
authors.initials: N
authors.lastname: Gogtay
authors.forename: Chhanda J
authors.initials: CJ
authors.lastname: Kapadia
authors.forename: Nabil
authors.initials: N
authors.lastname: Farah
authors.forename: Mangal S
authors.initials: MS
authors.lastname: Nagarsenker
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000737:chemistry* / Q000493:pharmacokinetics; D000328:Adult; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005227:Fatty Acids / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013607:Tablets; D014867:Water / Q000737:chemistry; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D005079:Excipients; D005227:Fatty Acids; D013607:Tablets; D014867:Water; C086409:glyceryl behenate; D008790:Metoprolol