Drug products, formulation development excipient selection

A preservative is a substance that prevents or inhibits microbial growth and extends the shelf life of the drug products. In most pharmaceutical drug products, only a few compounds are typically selected as preservatives. For efficiency, a generic method should be developed for the types of preservatives that are more commonly used. For example, butylated hydroxytoluene (BHT) is an antioxidant commonly used in many solid dosage formulations to retard oxidative degradation of the excipients. 

Excipients are additives that are included in a formulation, because they either impart or enhance the stability, delivery, and manufacturability of a drug product. Regardless of the reason for their inclusion, excipients are an integral component of a drug product and therefore need to be safe and well tolerated by patients. For protein drugs, the choice of excipients is particularly important because they can affect both efficacy and immunogenicity of the drug. Hence, protein formulations need to be developed with appropriate selection of excipients that afford suitable stability, safety, and marketability. 

In addition, simple binary studies with key excipients should be done to establish physical and chemical compatibility between the API and the selected excipient. These studies need not be elaborate, but will provide useful information to the formulator during the critical drug product development stage. 

Excipient and vendor selections can greatly influence the new drag development timeline, product performance, and acceptance of final products. Compendial excipients have composition consistent with monographs published in compendia such as USP-NF these are the better-characterized excipients. These excipients most likely possess desirable qualities and are preferred excipients for pharmaceutical formulations. Non-compendial excipients can also be used for drug products if they are supported by Type IV dmg master files (DMFs) in regulatory dossiers. Overall, a good excipient supplier should 29... 

Level C correlation This correlation describes a relationship between the amount of drug dissolved (e.g., percent dissolved in one hour) at one time point and one pharmacokinetic parameter [e.g., either area under the curve (AUC) or Cmaxl-Level C correlation is considered the lowest correlation level as it does not reflect the complete shape of the plasma concentration time curve. Similarly, a multiple Level C correlation relates one or more pharmacokinetic parameters to the percent drug dissolved at several time points of the dissolution profile and thus may be more useful. Levels B and C correlations can be useful in early formulation development, including the selection of the appropriate excipients, optimization of manufacturing processes, for quality control purposes, and characterization of the release patterns of newly formulated immediate-release and modified-release products relative to the reference. 

Process technology selection for the manufacture of amorphous solid dispersions requires consideration of the particular complexities of the drug and excipients. HME offers the possibility to manufacture drug products in a continuous, cost-effective manner, yet it presents unique challenges that must be tackled. Noting the significant interplay between formulation and process, a risk-based classification system has been developed to aid in the early assessment of dispersion success using melt extrusion. 

Obviously, each material in a formulation can be characterized in this way by use of instrumented press studies and Ileckel plot analysis in research and development. This approach can be of use to formulators in selecting specific excipients for specific drug entities. However, the characterization and performance of the final formulation are the critical measurements in the scale-up/production compaction operation. 

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