Development of Novel Combination Therapies

Hot-melt co-extrusion for the production of fixed-dose combination products with a controlled release ethylcellulose matrix core

“…The need for novel combination therapies, primarily focusing on fixed-dose combinations (FDC), has been reported by various authors and is seen as a driver for innovative drug development (Woodcock et al, 2011 andZhang et al, 2011). Besides their benefits in life 55 cycle management, FDC products have shown to improve patient adherence by decreasing the number of required pills and thus reducing the complexity of the medication regimen (Pan et al, 2008).…”

Challenges and Opportunities in Achieving Bioequivalence for Fixed-Dose Combination Products

“…FDCs are becoming popular treatment options because (a) increased patient compliance and adherence in diseases such as diabetes (1) and hypertension (2), (b) patient convenience and simplification of disease management such as AIDS and cardiovascular diseases, (c) reduced cost to the patient (one co-pay), and finally (d) FDC products provide an excellent opportunity for life cycle management of marketed drug products. These advantages of FDC products along with the possibilities of greater clinical efficacy due to additive or synergistic effect of each active, possibility of reduced dose of each active, and decrease in the occurrence of side effects make combination drug products a very attractive treatment option (3,4). However, careful considerations must be given to the mechanisms of action of the actives being considered for combination.…”

Median Effect Dose and Combination Index Analysis of Cytotoxic Drugs Using Flow Cytometry

“…Targeted therapies may offer enhanced efficacy, enhanced selectivity, and less toxicity. However, targeting selective molecules and pathways often induces the activation of redundant mechanisms and enhances the emergence of resistant cells due to selective pressure (Woodcock et al, 2011). This is one of the reasons why the effects of targeted agents are not durable when used alone, and often result in drug resistance and clinical relapse.…”

“…An increase in the number of these studies is expected in coming years, on the basis of emerging data with new agents, which is expanding our understanding of the molecular pathways important in cancer progression. (Woodcock et al, 2011). Tumor intracellular signalling pathway dependencies are being increasingly analyzed, and patients treated on the basis of resistance profile detected for specific drug combinations (Busch et al;Derenzini et al, 2009;Michiels et al, 2011).…”