Development of pressure-sensitive dosage forms with a core liquefying at body temperature

Eur J Pharm Biopharm. 2014 Apr;86(3):507-13. doi: 10.1016/j.ejpb.2013.12.008. Epub 2013 Dec 17.

Abstract

Pressure-sensitive dosage forms have been developed that are intended for pulsatile delivery of drugs to the proximal small intestine. The novel dosage forms are composed of insoluble shell and either a hard fat W32 or polyethylene glycol (PEG) 1000 core that are both liquidizing at body temperature. The release is triggered by predominant pressure waves such as contractions of the pylorus causing rupture of the shell and an immediate emptying of the liquefied filling containing the active ingredient. In consequence immediately after the trigger has been effective the total amount of the drug is intended to be available for absorption in the upper small intestine. Both core types were coated with a cellulose acetate film that creates a pressure-sensitive shell in which mechanical resistance is depending on the coating thickness. Results of the texture analysis confirmed a correlation between the polymer load of the coating and the mechanical resistance. The dissolution test performed under conditions of physiological meaningful mechanical stress showed that the drug release is triggered by pressure waves of ⩾300 mbar which are representing the maximal pressure occurring during the gastric emptying.

Keywords: Dissolution stress test; Drug-targeting; Gastric emptying; Liquid core formulation; Pressure-sensitive; Pylorus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Temperature* / drug effects
  • Body Temperature* / physiology
  • Chemistry, Pharmaceutical / methods*
  • Dosage Forms
  • Microspheres*
  • Pharmaceutical Vehicles / administration & dosage
  • Pharmaceutical Vehicles / chemistry*
  • Pressure
  • Solubility / drug effects
  • Stress, Mechanical
  • Triglycerides / administration & dosage
  • Triglycerides / chemistry*

Substances

  • Dosage Forms
  • Pharmaceutical Vehicles
  • Triglycerides
  • witepsol