Billions of soft gelatin capsules are made each year in various sizes and shapes, and in a variety of colors and color combinations. Their pharmaceutical applications are:
- As an oral dosage form of ethical or proprietary products for human or veterinary use.
- As a suppository dosage form for rectal use, or for vaginal use.
- As a specialty package in tube form, for human and veterinary single dose application of topical, ophthalmic, and ode preparations, and rectal ointments.
Soft gelatin capsules generally contain the medicament dissolved or dispersed in oils or hydrophilic liquids (i.e., fill liquid). The inherent flexibility of the soft gelatin capsule is due to the presence of plasticizers and residual moisture in the capsule shell. Thus, the soft gelatin capsule is a more dynamic system than conventional tablets. The atmospheric moisture may permeate into the capsule shell or into the fill liquid. The drug or fill liquid may migrate into the capsule shell, while the plasticizer or residual water in the gelatin shell can potentially migrate into the fill. Volatile components in soft gelatin capsules may escape into the atmosphere. It is these characteristics that must be considered when designing a shelf life stability program for soft gelatin capsules.
In most instances, the recommended storage conditions are stated on the label in which case it is imperative to maintain stability. Normally, the recommended storage conditions for empty capsule shells are 15 to 25°C and a relative humidity of between 35% and 65%. This condition is designed to minimize moisture absorption or loss, and the resultant changes in physical dimensions, during the encapsulation operation.
While there is no strict guidances for stability testing of soft gelatin capsules, there are a couple of guidelines available that will help evaluate the storage conditions and length of study required for specific formulations, including soft gelatin capsules. The "GCC Guidelines for Stability Testing of Drug Substances and Pharmaceutical Products" and the "Asean Guideline on Stability Study of Drug Product" documents are available on line at http://www.sgh.org.sa/PDF/GCC_STABILITY.pdf and http://www.hsa.gov.sg/publish/hsaportal/en/health_products_regulation/western_medicines/guidelines.html.
Both guidelines indicate that testing of soft gelatin capsules should be evaluated in terms of appearance (including brittleness), color, and odor of content, assay, degradation products, dissolution, microbial content, pH, leakage, and pellicle formation. Also, fill medium should be examined for precipitation and cloudiness.
In general, a drug product should be evaluated under storage conditions (with appropriate tolerances) that test the thermal stability, and if applicable, its sensitivity to moisture or potential for solvent loss. If it is determined that a particular product is heat sensitive, then these drug products should be stored under an alternative lower temperature condition which will eventually become the designated long-term storage temperature. For example, a 30°C storage condition versus a 40°C condition may be justified.
Unfortunately, there are no hard and fast rules to follow. Each product must be evaluated on its own characteristics and formulation make up.
[To respond to Mr. Ricchezza's Expert Opinion or to submit your own, please send us an e-mail.]