Preparation and evaluation of ritodrine buccal tablets for rational therapeutic use.
Ritodrine hydrochloride (RD-HCl) tablets containing alginate (AL) and lactose (LC) with or without microcrystalline cellulose (MC) as excipients were produced as a buccal dosage form. The RD-HCl (2 mg) tablets with AL/LC but no MC swelled and dissolved gradually in the in vitro dissolution test. The tablet showing the fastest dissolution and highest drug release rate, called Tablet A1, was selected as a tablet to show rapid and prolonged absorption. However, in the in vivo buccal absorption test using rats, it could not give a plasma concentration over the human minimal effective level (15 ng/mL). The modified tablet containing AL, LC, MC and RD-HCl (4 mg), named Tablet B/MC, showed better hardness and faster drug release. Tablet B/MC gave a plasma concentration over the human effective level within 15 min, and the plasma concentration was maintained at >15 ng/mL over 4 h. Moreover, the deconvolution analyses demonstrated that a prolonged high absorption rate could be achieved in vivo best with Tablet B/MC. Tablet B/MC improved the pharmacokinetic profile in comparison with Tablet A1 and the solution dosage form. The RD-HCl buccal tablets with AL, LC and MC as excipients are suggested to be possibly useful for the treatment of premature labor.
Department of Drug Delivery Research, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. Electronic address: onishi@hoshi.ac.jp.
Hiraku
H
Onishi
Department of Drug Delivery Research, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Kei
K
Yumoto
Department of Drug Delivery Research, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Osamu
O
Sakata
D000278:Administration, Buccal; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000464:Alginates / Q000737:chemistry; D000818:Animals; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D005079:Excipients / Q000737:chemistry; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006244:Hardness; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D007785:Lactose / Q000737:chemistry; D008297:Male; D008954:Models, Biological; D007752:Obstetric Labor, Premature / Q000188:drug therapy*; D065568:Oral Mucosal Absorption; D010316:Particle Size; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012312:Ritodrine / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D015149:Tocolytic Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
D058666:Adrenergic beta-2 Receptor Agonists; D000464:Alginates; D005079:Excipients; D006603:Hexuronic Acids; D013607:Tablets; D015149:Tocolytic Agents; D020723:Glucuronic Acid; D002482:Cellulose; D012312:Ritodrine; D007785:Lactose; C109691:microcrystalline cellulose
Absorption rate; Buccal tablet; Dissolution; Hardness; Plasma level; Ritodrine hydrochloride