Issues to consider in the pharmaceutical development of a cardiovascular polypill

Abstract

The pharmaceutical development of a cardiovascular polypill presents several unique challenges. The selection of the type and number of active drugs to be incorporated requires important consideration of clinical, pharmaceutical and commercial issues, and the final decision with regard to the polypill's components depends on how these issues are prioritized. Once the drug combination has been chosen, developers must determine which pharmaceutical formulation should be used. The most appropriate method of drug delivery can vary markedly and depends on the characteristics of the drugs to be combined. Finally, careful consideration of how to gather the type of information required by regulatory agencies before a particular polypill can be approved for use in the general population is crucial. Although the association of multiple, active ingredients in a single dosage form would represent a major step forward in the prevention of cardiovascular conditions, a careful evaluation of all the above-mentioned variables and a well thought-out development plan is mandatory to maximize the chances of success.

Potential impact of single-risk-factor versus total risk management for the prevention of cardiovascular events in Seychelles

“…Ninth, some believe that CV risk prediction scores should factor in the occurrence of CV events over longer periods, perhaps 30 years instead of 10. 41 Furthermore, the indications for the use of a polypill are still being debated, 15,42,43 but evidence on the polypill's applicability and effectiveness is emerging. 15,18 Finally, with a fairly high GDP per capita and a small population, Seychelles is hardly representative of the majority of African countries.…”

A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy (‘polypill’) on cardiovascular risk factors

“…The most novel aspect of this proposal has been to offer treatment to individuals whose risk factors are below usual treatment levels, but who are nevertheless at high risk of cardiovascular disease because of their age and gender. There are a number of issues to consider in choosing the exact formulation of a polypill, and a greater number of active components promises greater effectiveness, but poses greater technical problems in developing the polypill (13). As a result of this, a number of variations of the polypill are currently under …”

The Concept of the Polypill in the Prevention of Cardiovascular Disease

“…Sanz and Fuster's concern about limiting the number of formulations of the combination pill is well founded because from a technical standpoint there is an almost linear relationship between the number of active components in the polypill and the difficulty of formulation. 23 The difficulty of formulation relates to the different characteristics of each component with respect to chemical and physical stability. Combining compounds with differing solubility and sensitivity to heat and moisture requires significant development time and cost.…”

“…The use of certain components in very low doses (such as ramipril at 2.5 mg) combined with another compound at a much higher dose (such as atenolol at 100 mg) causes technical problems with the analytical methods used in purification and bioanalytics. 23 The formulation of a combination polypill also has illustrated the potential for drug-drug interactions and issues with bioavailability. It has been demonstrated that the plasma concentration and bioavailability of simvastatin, when taken as part of the PolycapÒ pill (simvastatin 20 mg, aspirin 100 mg, hydrochlorothiazide [HCTZ] 12.5 mg, atenolol 50 mg, ramipril 5 mg), was significantly lower than simvastatin taken alone.…”