Liquid Formulation—Generic

For a liquid or semi-solid pharmaceutical dosage form, it is crucial to include a preservative in the formulation. Commonly used preservatives in these systems include sodium benzoate, EDTA, sorbic acid, and parabens. A generic HPLC method is also recommended for the preservatives used in liquid formulations for routine monitoring to ensure the stability of the preservative itself and it must be validated specific to its use with the dosage form. (See chapters on Sample Preparation and Method Development.)... 

A preservative is a substance that extends the shelf-life of drug products by preventing oxidation or inhibiting microbial growth.14 Preservatives must be monitored in the products since they are considered to be active components. Generic HPLC assays are typically developed for preservatives such as buty-lated hydroxytoluene (BHT), an antioxidant for solid dosage forms, and antimicrobials such as parabens, sodium benzoate, or sorbic acid in liquid formulations. For these additive components, typical assay specifications are 85-115% of label claim. 

Theeuwes, F. and Yum, S.I. (1976). Principles of the design and operation of generic osmotic pumps for the delivery of semisolid or liquid drug formulations. Ann. Biomed. Eng. 4 343-353. 

Patents have been granted for innovations involving the preparation and activities of broad-spectrum antimicrobial emulsions from 1977 (Sippos) to 2000 (Baker). All of these patents claim antibacterial activity, but all involve additives in the non-aqueous phase of the emulsion that are known to be antibacterial alone and before emulsification. Wide spectrum applications for these nanoemulsions have been claimed with positive results for bacteria, fungi, and viruses. The term nanoemulsion is used in US patents discussed below, but the generic term for the product of an emulsification (Gooch 2002, 1980) of a liquid within a liquid is an emulsion. United States patents 6,015,832 and 5,547,677 were examined and formulations in key claim statements were reproduced, and tested using standard methods for effectiveness. Additional patents listed in the reference section were reviewed as part of this study. 

Figure 12.19 Drug delivery curves obtained with an implantable osmotic pump [30], Reprinted from F. Theeuwes and S.I. Yum, Principles of the Design and Operation of Generic Osmotic Pumps for the Delivery of Semisolid or Liquid Drug Formulations, Ann. Biomed. Eng. 4, 343, 1976, with permission of Biomedical Engineering Society...

An early preformulation decision is generally made regarding the final formulation, whether it will be liquid or lyophilized. It is this a choice that determines which excipients wiU be needed (Table 4), as liquid and lyophilized products require different excipients. Several products are available in both forms. As clinical supplies wiU often require a placebo, unless the product is developed as a generic equivalent, these formuations will be made without the active ingredient. 

AEROSOLS. A generic term applied to packs of various liquid products under pressure. -Muminuni alloy cans have been used to package aerosol formulations. See also Ref (3) pp. 110. 239. 

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