In Vivo Performance of an Oral MR Matrix Tablet Formulation in the Beagle Dog in the Fed and Fasted State: Assessment of Mechanical Weakness

• Published in: Pharmaceutical research Vol. 25; no. 5; pp. 1075 - 1084
• Main Authors: McInnes, Fiona, Clear, Nicola, Humphrey, Michael, Stevens, Howard N E
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.05.2008; Springer; Springer Nature B.V
• Subjects: Animals; Area Under Curve; Azepines - administration & dosage; Azepines - chemistry; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedical research; Biomedicine; Chemistry, Pharmaceutical; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - chemistry; Diet; Dogs; Drug Compounding; Drug dosages; Fasting - metabolism; Gastrointestinal Transit; General pharmacology; Hardness Tests; Injections, Intravenous; Medical Law; Medical sciences; Pharmaceutical Solutions; Pharmaceutical technology. Pharmaceutical industry; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Quinolines - administration & dosage; Quinolines - chemistry; Radioisotopes - pharmacokinetics; Research Paper; Samarium - pharmacokinetics; Solubility; Tablets; matrix tablet; food effects; gamma scintigraphy; IVIVC; pharmacoscintigraphy; Performance evaluation; Fissipedia; Carnivora; Pharmaceutical technology; Oral administration; Scintigraphy; Matrix tablet; In vivo; Vertebrata; Mammalia; Animal; Formulation; Dosage form; Performance; Fast; Dog; Food
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-007-9462-6

Purpose To evaluate the behaviour of an oral matrix modified release formulation in the canine gastrointestinal tract, and establish if a mechanical weakness previously observed in clinical studies would have been identified in the dog model. Materials and Methods In vitro release profiles were obtained for two modified release matrix tablets containing UK-294,315, designed to release over either 6 (formulation A) or 18 (formulation B) hours. Tablets were labelled with 153 samarium and in vivo pharmacoscintigraphy studies were performed in four beagle dogs in the fasted state for both formulations, and following ingestion of an FDA high fat meal for formulation B. Results The matrix tablet formulations displayed significantly different in vitro release profiles ( F 2  < 50), with time to 80% release for formulation A and B of 406 and 987 min respectively. Complete in vivo disintegration occurred at 339 ± 181 and 229 ± 171 for formulation A and B respectively in the fasted state, and at 207 ± 154 min for formulation B in the fed state, in disagreement with in vitro release. Conclusion The fed/fasted dog model would have predicted a lack of physical robustness in the matrix tablet formulation B, however it would not have predicted the clear fed/fasted effects on performance observed previously in man.