It is estimated that only 1 out of 10 drug molecules that are selected for development and undergoes various preclinical and clinical development activities ultimately reaches the market. Because of such an attrition rate, drug companies are often forced to conservere sources during initial development and bring a product to the market that may not have optimal pharmaceutical and clinical attributes. This approach also leads to faster availability of new therapies to patients. After the initial launch, further development activities leading to superior products, known as the product LCM, continue. The LCM may lead to new dosage forms and delivery systems, new dosing regimen, delivery routes, patient convenience, intellectual property, and so on. An LCM program is considered successful only if it leads to better therapy and patient acceptance. There are numerous examples of successful LCM through the development of prolonged-release formulations. Development of nifedipine (Procardia® XL, Pfizer), diltiazem (Cardizem CD®, Aventis), and bupropion HCl (Wellbutrin SR® and XL®, GSK) prolonged-release products that not only provided more convenient and better therapy to the patients by reducing dosing frequency but at the same time greatly increased sales of the products are well-known examples. Even old compounds like morphine and oxycodone were turned into important products by the development of more convenient prolonged-release formulations (MS Contin® and Oxycontin®, respectively; Purdue Pharma).
Many of the future LCM opportunities may come through bioavailability enhancement. Solid dispersion, microemulsion, soft gelatin capsule formation, solubilization, lipid-based DDSs (drug-delivery system), nanoparticle or nanocomposite formation, etc., are some of the common bioavailability approaches that can be utilized for LCM. Development of Lanoxicaps® by Burroughs-Wellcome in 1970s by encapsulating digoxin solutions in soft gelatin capsules is a classic example of LCM by bioavailability enhancement and better pharmacokinetic properties. The development of a microemulsion preconcentrate formulation by Novartis (Neoral®), where the variability in plasma and the effect of food were reduced greatly, is another well-known example.
Life-cycle management through the development of fixed combination products, where two or more drugs are developed or copackaged into a single entity, is gaining increased popularity. The fixed combination products often provide synergistic effects, better therapy, patient compliance, patient convenience, increased manufacturing efficiency, and reduced manufacturing cost. However, a clear risk/benefit advantage is essential for the successful LCM by combination products; mere patient convenience may not be sufficient.
Common justifications for the development of fixed combination products include improvement of activity such as synergistic or additive effect, improved tolerance by reduced dose of individual ingredients, broadening of activity spectrum, improvement of pharmacokinetic properties, and simplification of therapy for the patient.
The development of oral dosage forms that disintegrate or dissolve in the mouth is providing LCM opportunities for pediatric, geriatric, or bedridden patients who have difficulty in swallowing. They are also being used by active adult patients who may not have ready access to water for swallowing tablets or capsules.
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