BIOEQUIVALENCE EVALUATION OF ORALLY DISINTEGRATING STRIPS OF RIZATRIPTAN IN MALE VOLUNTEERS UNDER FASTING CONDITIONS Original Article NIDHI SAPKAL 1,2 , ANWAR DAUD 2 , MINAL BONDE 2 , MANGESH GAWANDE 2 , NILAMBARI GURAV 3* 1 Gurunanak College of Pharmacy, Kamptee Road, Nagpur, Maharashtra, India 440026, 2 Zim Laboratories Limited, Kalmeshwar, Nagpur, Maharashtra, India 441501, 3* P. E. S.’s Rajaram and Tarabai Bandekar College of Pharmacy, Goa, India 403401 Email: nilagurav@rediffmail.com Received: 25 Mar 2021, Revised and Accepted: 29 Jul 2021 ABSTRACT Objective: A randomized, open-label, balanced, two-treatment, two-period, two-sequence, single-dose, crossover bioequivalence study comparing Rizatriptan 10 mg Orally Disintegrating Strips (ODS, test) with that of established Oral Lyophilisate Rizatriptan 10 mg, Maxalt-MLT® (reference) was conducted in 24 healthy male volunteers under fasting conditions. A single oral dose of 10 mg Rizatriptan was administrated to each volunteer. Methods: Plasma concentrations of Rizatriptan were determined by a validated LC-MS/MS bioanalytical method. The plasma concentrations of Rizatriptan were considered for statistical analysis and for establishing bioequivalence. Pharmacokinetic analysis was done by using the non- compartmental method. Pharmacokinetic parameters Cmax, AUC0→t, AUC 0→∞, t1/2, Tmax, and Ke1 were estimated for each subject and each treatment. Results: Ninety percent confidence intervals (90% CI) calculated for the ratio of AUC0→t, AUC0→∞, and Cmax values for the test and reference formulations were 96.91-110.30%, 96.24-109.07%, and 90.37-113.56%, respectively for Rizatriptan. The 90% CIs of AUC0→t, AUC0→∞, and Cmax values were totally within 80-125%. Conclusion: Based on a statistical analysis of the results, both formulations of Rizatriptan 10 mg, were found to be bioequivalent in terms of rate and extent of absorption under fasting conditions. Keywords: Rizatriptan, Orally Disintegrating Strips, Pharmacokinetics, Bioequivalence, Migraine © 2021 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2021v13i5.41602. Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Migraine is a common neurologic disorder with a paroxysmal character. Lost work productivity following migraine attacks severely affects both patients and society. This condition is most prevalent during the most economically productive years of the person, with a peak at ~ 40 y of age. Attacks of moderate or severe headache associated with nausea, vomiting, photophobia, or phonophobia occur in 3% to 6% of males and 13% to 18% of females [1-5]. Migraine attacks can also lead to disabilities and affect the quality of relationships, social behavior, economic assets, emotional well-being, and overall health of the patients [6-8]. Thus, effective treatment of acute migraine attacks is always looked for in clinical practices for improving health-related quality of life and economic growth [9]. Rizatriptan is an anti-migraine drug belonging to the class of serotonin receptor agonist, 5-HT1. Rizatriptan is indicated for the acute treatment of migraine with or without aura in adults [10]. The 10-mg dose was found to be more effective than the 5-mg dose in the case of adults and pediatric patients [10, 11]. Rizatriptan is absorbed quickly after oral administration. It is absorbed completely from the gastrointestinal tract and achieves shorter Tmax than other triptans [12]. It exhibits a favorable tolerability profile and greater patient compliance over other triptans as well [13]. However, mean oral absolute bioavailability is about 45% due to hepatic first-pass metabolism of the drug [12]. Rizatriptan is available in the form of conventional swallowable tablets and orally disintegrating tablets (ODT). The Tmax for Rizatriptan in tablet form is 1-1.5 h and about 1.6-2.5 h for ODT. The onset of the effect of Rizatriptan occurs after at least 30 min with 10 mg oral tablet [14]. The slower Tmax may be responsible for delayed onset of action associated with formulations like ODT. Further, ODT s are highly friable and fragile as they are manufactured using lyophilization or low compression technology, therefore, it is difficult to handle them during administration and transportation. Orally disintegrating strip (ODS) is a novel dosage form that overcomes the limitations of ODT. It consists of thin, rectangular film that dissolves instantaneously when kept on the tongue without requiring the intake of water [15-18]. Additionally, these films are flexible and do not break or crumble during handling and transportation. These features make ODS, a convenient and consumer-friendly dosage form [18]. The ODS technology can therefore serve as a very useful option for delivering drugs for migraine. During migraine attacks, the patient is under huge distress and any change in the position of the head may worsen the pain and symptoms like nausea and vomiting. The easy administration and fast dissolving feature of ODS bring quick relief during acute migraine attacks and avoid the need for injectable formulations. Considering the clinical aspects of 'migraine' and related pathologies, immediate release of medicament is a must for quick onset of action and relief. Therefore, considering various attributes of ODS technology, Rizatriptan ODS was developed to offer other beneficial and effective options to the consumers. The main objective of the present study was to determine bioequivalence between the novel ODS containing 10 mg Rizatriptan (test product, T) against Maxalt-MLT® (Oral Lyophilisate, 10 mg Rizatriptan, reference product, R) under fasting conditions in healthy male volunteers. The safety and tolerability of a single oral dose of Rizatriptan ODS and Oral Lyophilisate were also monitored. MATERIALS AND METHODS A randomized, open-label, balanced, two-treatment, two-period, two-sequence, single-dose, crossover study was conducted. All of the subjects were randomly assigned to one of two sequences of the two formulations: ODS containing Rizatriptan 10 mg (test product) and Oral Lyophilisate containing Rizatriptan 10 mg (reference product). The baseline evaluations were performed before dosing. The study protocol was approved by the Independent Ethics Committee (Ethics Committee No. ECR/112/Indt/MH/2013). The study was conducted following the Declaration of Helsinki (Ethical Principles for Biomedical Research involving Human Male Subjects, International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 13, Issue 5, 2021