Preparation and Evaluation of Medicated Intra-articular Delivery Systems

Abstract

Rheumatoid arthritis (RA) is an auto-immune disorder that results in chronic, systemic inflammatory conditions. It affects many organs and tissues all over the body, but principally attacks the flexible synovial joints. RA is mainly manifested by an irreversible destruction of the synovium, causing a painful swelling, which can eventually leads to loss of the joint space, bone erosion and joint deformity.

Triamcinolone acetonide (TA) is a synthetic, long-acting corticosteroid, commonly used in RA treatment due to its anti-inflammatory and immune-modulatory effect. It belongs to class IV biopharmaceutical classification system (BCS), therefore TA exhibits formulation-related constraints, in addition to its severe side effects accompanying its systemic administration. Therefore, localizing TA into the target joint via intra- articular (IA) administration can overcome these problems. However, rapid drug efflux from the joint cavity into the systemic circulation can occur following IA injection as a result of the leaky ultra-structure nature of the synovium. Therefore, frequent injections are required to reach the desired therapeutic drug effect, which may lead to patient discomfort, a high risk of infection and a possibility to develop joint injury.

Hence, the aim of work in this thesis was to develop novel delivery systems loaded with TA, acquiring appropriate characteristics for effective IA delivery, targeting to prolong its residence time within the affected joint cavity for efficient RA treatment.

Therefore the work in this thesis is divided into three chapters: