Preparation of Controlled Release Tablets of TA-5707F with Wax Matrix Type and Their in Vivo Evaluation in Beagle Dogs

• Published in: Biological & pharmaceutical bulletin 1995/07/15, Vol.18(7), pp.984-989
• Main Authors: YAMAKITA, Hirokazu, MAEJIMA, Toru, OSAWA, Takashi
• Format: Article
• Language: English
• Subjects: Animals; bioavailability; Biological and medical sciences; Biological Availability; Chemical Phenomena; Chemistry, Physical; Cholinergic Antagonists - pharmacology; Delayed-Action Preparations; dissolution; Dogs; Drug Interactions; food; Food-Drug Interactions; General pharmacology; Hardness Tests; Histamine H1 Antagonists - administration & dosage; Histamine H1 Antagonists - pharmacokinetics; In Vitro Techniques; Male; Medical sciences; Niacinamide - administration & dosage; Niacinamide - analogs & derivatives; Niacinamide - pharmacokinetics; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Solubility; Tablets; wax matrix; Waxes
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.18.984

Studies on controlled release dosage forms were conducted by using waxy materials for a newly developed anti-allergy drug, 6-methyl-N-(1H-tetrazol-5-yl)-2-pyridinecarboxamide (TA-5707F), which is not maintained at an effective level in blood for a long duration. Four kinds of tablets were prepared by changing the amount of hydrogenated oil (K3 wax) and polyethyleneglycol-6000 in the tablets. Then, they were administered orally to beagle dogs, and the TA-5707F concentration in the plasma was determined by a HPLC method. The pharmacokinetic parameters were estimated and compared with the results of the in vitro dissolution test determined by the JP paddle method and by the disintegration method. The linearity between the in vivo mean dissolution time (MDT) and in vitro MDT was good in both in vitro dissolution methods. However, the MDTs obtained by the disintegration method were one-third of the in vivo MDT, while those obtained by the paddle methods were 3 times higher. This suggests that both the diffusion of TA-5707F through the waxy matrix and the erosion of the wax matrix caused by the gastrointestinal (GI) tract mobility contributed to the in vivo dissolution mechanism. The blood levels were very low when the tablet was administered after giving food. The prolongation of resident time in the stomach and the low solubility of TA-5707F in an acidic medium seemed to be related to the phenomena. By the depression of GI motility using propantheline bromide, the blood levels could be markedly prolonged and the area under the plasma concentration-time curve (AUC) increased 1.3 times.