Formulation strategies in developing an oil-filled capsule for time-delayed release

A rational approach was adopted in the design of a novel controlled release system aimed at delivering hydrophobic drugs in a wholly time-dependent manner. A swellable, rupturable system in which hydrophobic drugs were solubilised in vegetable oils was proposed. Two main components of the system, the swelling agent low-substituted hydroxypropylcellulose (grade LH-21) and brittle outer coating of ethylcellulose (EC) were individually characterised. Upon contact with water, LH-21 swelled rapidly and to a great extent, exemplified by using simple apparatus to measure water uptake and swelling force. Mixing it with other excipients such as vegetable oils, surfactants and drugs tended to decrease LH-21 water uptake rate and subsequent force generation rate. Solution-cast EC films enabled thorough investigations into the mechanical integrity and physicochemical properties of the proposed outer coating of the capsule. Plasticisation decreased the strength while increasing the malleability of the film while increasing polymer content toughened the film and increased its elastic modulus. These findings were extrapolated to the construction of the dosage form in its two configurations. The first involved filling a hard gelatin capsule with a dispersion of LH-21 in corn oil and coating it with EC. In the second, a gelatin-based tablet separated LH-21 and corn oil. Burst release following a lag time was obtained with both configurations. In general, decreasing the LH-21 concentration and increasing the EC coating level prolonged the lag time. A limit of LH-21 concentration was identified below which more sustained release was observed indicating sufficient LH-21 was required to efficiently expel the capsule fill. Problems with leakage of the oil component were addressed in the hope of manufacturing reproducible dosage forms. Improvements to the construction process are essential if successful drug delivery is to be achieved.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral-pg

Grantor dc:publisher.institution

University of Strathclyde

Year dc:date.issued

2005

Author dc:creator

• Hodges, Lee Ann

DOI

10.48730/s0ap-tq91

Identifier

uk.bl.ethos.416192
T11188

OAI identifier oai:identifier

oai:strathclyde:z316q158b