Drug product factors affecting

Table 6 Factors Affecting Drug Product Safety, Effectiveness, and Reliability...

Intramuscularly administered products typically form a depot in the muscle mass from which the drug is slowly absorbed. The peak drug concentration is usually seen within 1-2 hours. Factors affecting the drug-release rate from an IM depot include the compactness of the depot (the less compact and more diffuse, the faster the release), the rheology of the product, concentration and particle size of drug in the vehicle, nature of the solvent or vehicle, volume of the injection, tonicity of the product, and physical form of the product. 

A biologically important factor affecting drug absorption is drug metabolism or reaction coincident with diffusion across a membrane. The reaction often produces inactive or less potent products than the parent drug. It is conceivable that the reaction will also reduce the drug flux into the systemic circulation. We are interested in the effect of reaction on membrane diffusion. 

Water uptake causes a host of problems in drug products and the inactive and active ingredients contained in them. Moisture uptake has been shown to be an important factor in the decomposition of drug substances [1-8]. Moisture has also been shown to change surface properties of solids [9,10], alter flow characteristics of powders [11,12], and affect the compaction properties of solids [13]. This chapter discusses various mathematical models that can be used to describe moisture uptake by deliquescent materials. 

Solubility, dissolution rate, and intestinal permeability, are the major bio-pharmaceutic factors that affect the rate and extent of absorption of an oral drug product. Particularly for water insoluble drugs that have generally high membrane permeability (BCS Class II), dissolution, and dose are the most critical factors affecting the rate and the extent of oral absorption. 

The FDA s dehnition of comparability protocol is a well-defined, written plan for assessing the effect of specific CMC changes in the identity, strength, purity, and potency of a specific drug product as these factors relate to the safety and effectiveness of the product. A comparability protocol describes changes that are covered under the protocol and specifies the tests and studies that will be performed, including analytical procedures that will be used, and acceptance criteria that will be achieved to demonstrate that specified CMC changes do not adversely affect the product. ... 

Factors Affecting Drug Substance and Product Stability... 

The Role of DPls in Therapy briefly discusses factors affecting the therapeutic profiles of drugs delivered by DPI devices. The article concludes with The Burgeoning DPI Industry, which surveys the DPI products on the market in 1999 and a selection of those known to be under development. Thoughts on the potential of the DPI dosage form in future therapeutic applications conclude the article. 

Microbial stability is one of the factors affecting drug product reliability. Under design and interpretation of stability studies, the Center for Drugs and Biologies... 

Factors affecting the delivery include the physical form of the drug, the entry into the body, the design and the formula of the product. This may depend on the physicochemical properties of the excipients, the control of the drug-excipient interaction at the absorption site. Thus, polysaccharides may play an essential role for effectiveness and reliability of the different drug delivery systems. 

Pharmacokinetics is the study of how the body affects an administered drug. It measures the kinetic relationships between the absorption, distribution, metabolism, and excretion of a drug. To be a safe and effective drug product, the drug must reach the desired si te of therapentic activity and exist there for the desired time period in the concentration needed to achieve the desired effect. Too little of the drug at such sites yields no positive effect (MTC) leads to toxicity. For intravenous administration there is no absorption factor. Total body elimination includes both metabolic processing and excretion. 

Each manufacturing platform has unique characteristics and complexity in terms of unit operations. Table 2.6 presents a fairly comprehensive (but by no means exhaustive) list of unit operation, process parameters, and quality attributes. Since more than one platform technology can be used to manufacture a drug product, selection of the most appropriate manufacturing platform is affected by many factors, such as ... 

---