Semisolid drugs products

For liquid or semisolid drug products such as parenterals, emulsions, suspensions, dermal creams, etc., the issue of "direct exposure" is not clearly addressed and can be somewhat confusing. The ICH guideline states, "Where practicable when testing samples of the drug product outside the primary pack, these should be presented in a way similar to the conditions mentioned for the drug substance."... 

Ritonavir is a product of Abbott Laboratories Ltd. for the treatment of HIV and is marketed as Norvir , in liquid and semisolid capsule formulations. It received FDA approval for market launch in march 1996, at which time only one polymorphic form of Ritonavir (Form I) was known. Two years later in early 1998 a laboratory responsible for testing the formulated product in the US reported dissolution test failures of the semisolid capsules, and noted that drug product had precipitated out of solution. A new polymorphic form had been discovered that was thermodynamically more stable than the existing form and approximately 5 times less soluble in the formulation. Figure 7. 

Formal Stability Studies — Long-term and accelerated (and intermediate) studies undertaken on primary or commitment batches according to a prescribed stability protocol to establish or confirm the retest period of a drug substance or the shelf life of a drug product. Impermeable Containers — Containers that provide a permanent barrier to the passage of gases or solvents (e.g., sealed aluminum tubes for semisolids, sealed glass ampoules for solutions). 

The key parameter for any drug product is its efficacy as demonstrated in controlled clinical trials. The time and expense associated with such trials make them unsuitable as routine quality control methods. Therefore, in vitro surrogate tests are often used to assure that product quality and performance are maintained over time and in the presence of change. A variety of physical and chemical tests commonly performed on semisolid products and their components (e.g., solubility, particle size and crystalline form of the active component, viscosity, and homogeneity of the product) have historically provided reasonable evidence of consistent performance. More recently, in vitro release testing has shown promise as a means to comprehensively assure consistent delivery of the active component(s) from semisolid products. 

The higher viscosity of semisolid dosage forms and transdermal systems may cause the rate of migration of leachable substances into these dosage forms to be slower than for aqueous solutions. Due to extended contact, the amount of leach-ables in these drug products may depend more on a leachable material s affinity for the liquid/semisolid phase than on the rate of migration. 

Pharmacodynamic (PD) studies are also performed to estimate the bioavailability and bioequivalence of drugs from topically applied semisolids. In this case, known therapeutic responses from drug products such as skin blanching due to vasoconstrictor effects caused by corticosteroids and transepidermal water loss caused by retinoids are measured and compared between the test and reference... 

The physical form of a drug product that is pourable displays Newtonian or pseudoplastic flow behavior and conforms to its container at room temperature. In contrast, a semisolid is not pourable and does not flow at low shear stress or conform to its container at room temperature [12], According to its physical characteristics, liquid dosage forms may be dispersed systems or solutions. 

Long-chain unsaturated oils such as fatty acid esters are used in a number of semisolid and liquid products. It is known from the use of these oils that the double bonds in their chemical structure can react with oxygen to form peroxides and/or hydroperoxides. Some compendial monographs for these materials will have specifications to limit the level of peroxide for this reason. For active ingredients that are easily oxidized, these excipients may need to be avoided to minimize the catalytic oxidation of the active ingredient and to maximize the stability of the drug product. 

Bracketing design is applicable to most types of drug products, including immediate- and modified-release oral solids, liquids, semisolids, and injectables. Certain types of drug products, such as MDIs, DPIs, and transdermal delivery systems, may not be amenable to, or may need additional justification for, bracketing design. 

Injectibles are in-situ semisolid drug depots that have been developed for drug delivery. This system has overcome several of the limitations associated with other drug-delivery systems discussed in preceding subsections. Injectibles are composed of biodegradable products that are injected into the body through a syringe once introduced into the body, these products solidify to form a semisolid depot [75]. Several types of... 

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