title: Controlled release of ropinirole hydrochloride from a multiple barrier layer tablet dosage form: effect of polymer type on pharmacokinetics and IVIVC.
abstract: The purpose of the present study was to control in vitro burst effect of the highly water-soluble drug, ropinirole hydrochloride to reduce in vivo dose dumping and to establish in vitro-in vivo correlation. The pharmacokinetics of two entirely different tablet formulation technologies is also explored in this study. For pharmacokinetics study, FDA recommends at least 10% difference in drug release for formulations to be studied but here a different approach was adopted. The formulations F8A and F9A having similar dissolution profiles among themselves and with Requip® XL™ (f 2 value 72, 77, 71 respectively) were evaluated. The C max of formulation F8A comprising hypromellose 100,000 cP was 1005.16 pg/ml as compared to 973.70 pg/ml of formulation F9A comprising hypromellose 4000 cP irrespective of T max of 5 and 5.75 h, respectively. The difference in release and extent of absorption in vivo was due to synergistic effect of complex RH release mechanism; however, AUC0-t and AUC0-∞ values were comparable. The level A correlation using the Wagner-Nelson method supported the findings where R (2) was 0.7597 and 0.9675 respectively for formulation F8A and F9A. Thus, in vivo studies are required for proving the therapeutic equivalency of different formulation technologies even though f 2 ≥ 50. The technology was demonstrated effectively at industrial manufacturing scale of 200,000 tablets.
authors.affiliation: Lupin Ltd. (Research Park), 46A/47A, Nande Village, Mulshi Taluka, Pune, 411 042, Maharashtra, India. nikhilmalewar@lupinpharma.com
authors.forename: Nikhil
authors.initials: N
authors.lastname: Malewar
authors.forename: Makarand
authors.initials: M
authors.lastname: Avachat
authors.forename: Varsha
authors.initials: V
authors.lastname: Pokharkar
authors.forename: Shirish
authors.initials: S
authors.lastname: Kulkarni
mesh_terms: D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018491:Dopamine Agonists / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004304:Dosage Forms; D005079:Excipients / Q000737:chemistry; D007211:Indoles / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013607:Tablets
chemical_list: D018491:Dopamine Agonists; D004304:Dosage Forms; D005079:Excipients; D007211:Indoles; D011108:Polymers; D013607:Tablets; C046649:ropinirole
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