Comparison of the mechanical destructive force in the small intestine of dog and human

• Published in: International journal of pharmaceutics Vol. 237; no. 1; pp. 139 - 149
• Main Authors: Kamba, Masaharu, Seta, Yasuo, Kusai, Akira, Nishimura, Kenji
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 26.04.2002; Elsevier
• Subjects: Administration, Oral; Adult; Animals; Biological and medical sciences; Biomechanical Phenomena; Compressive Strength; Destructive force; Dogs; Gastrointestinal transit; General pharmacology; Humans; Intestine, Small - metabolism; Intestine, Small - physiology; Male; Medical sciences; Middle Aged; Pharmaceutical Preparations - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Small intestine; Stomach; Stress, Mechanical; Tablets - chemistry; Tablets - pharmacokinetics; Teflon; Teflon; Gastrointestinal transit; Stomach; Small intestine; Destructive force; Human; Fissipedia; Carnivora; Destruction; Digestive system; Controlled release form; Crushing; Oral administration; Normal; Blood plasma; Vertebrata; Mammalia; Mechanical degradation; Dosage form; Solid form; Tablet; Mechanism of action; Dog; Comparative study
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(02)00043-1

The purpose of this study was to evaluate the destructive force that oral solid dosage forms receive in the small intestine of dogs and humans. Information on the mechanical destructive forces of the gastrointestinal tract (GI) helps formulation design research in the following way: (1) to improve the predictability of the dissolution test since in vivo drug release is affected by not only agitation intensity but also mechanical stress; (2) to design safe and robust products by avoiding dose-dumping or unintended drug release at an inadequate site; (3) to better understand the species difference in bioavailability by comparing the destructive forces against dosage forms in the GI of dogs with those of humans. “Destructive force Dependent Release System” (DDRS) was developed to measure the mechanical destructive forces of the GI tract by using highly hydrophobic Teflon powder. In a DDRS, a marker drug contained in the core tablet is released only when the DDRS receives a force larger than its pre-determined crushing strength. DDRS-Small Intestine (DDRS-SI), a modified DDRS, was prepared for targeting the small intestine. DDRS-SI was encapsulated in starch capsules (Capill®) and then the capsules were coated with an enteric film (DDRS-SI-Ecap). The capsules were administered to six dogs and nine human volunteers. Both dogs and human volunteers crushed a DDRS-SI having a crushing strength of 1.2 N. Therefore, these controlled-release formulations should withstand a destructive force of 1.2 N when they pass through the small intestine.