Controlled Release of Ropinirole Hydrochloride from a Multiple Barrier Layer Tablet Dosage Form: Effect of Polymer Type on Pharmacokinetics and IVIVC
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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.
KEY WORDScontrolled release polymer in vitro–in vivo correlation (IVIVC) multiple barrier layer tablets pharmacokinetics ropinirole hydrochloride (RH)
Authors are thankful to Lupin Bioresearch Centre, Pune, India for their contribution in pharmacokinetic studies.
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.
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