Formulations, liquid excipients

IMPORTANCE OF EXCIPIENT SELECTION IN THE PROCESS OF ORAL LIQUID FORMULATION DEVELOPMENT... 

EXCIPIENTS USED IN ORAL LIQUID FORMULATIONS Solubilizers... 

Choosing an acceptable preservative when developing an oral liquid formulation is primarily limited by the number of approved excipients. As Table 10 demonstrates, there are many preservatives listed in the FDA inactive ingredient guide for dosage forms other than oral liquids however not many have been commonly used in oral solutions or suspensions. 

The oxidation of an API in an oral liquid formulation can be difficult to control due to the trace amounts of impurities, which may be present from the API or excipient vendor, and oxidation and photolysis have relatively low activation energies (2-12 Kcal/mol) compared to solvolysis, dehydration, and polymorphic transformations (10-56 Kcal/mol) (Table 11) (10). 

The long-term stability of an oral liquid formulation can also be affected by a number of unexpected reasons. Contamination by solvents used during the tank cleaning or even in the manufacture of excipients or API can be a source of instability of an oral solution. Uncontrolled levels of Class I, II, or III solvents could lead to the rejection of a batch or an excipient vendor. Class III solvents have a permitted daily exposure of 50 mg or less per day. (See the International Conferences on Harmonization, Impurities Guidelines for Residual Solvents. Q3C, Federal Register 1997 62(247) 67377 and also http //www.fda.gov/cvm/Guidance/guidelOO.PDF). 

Reed RA, Harmon P, Manas D, Wasylaschuk W, Galli C, Biddell R, Bergquist PA, Hunke W, Templeton AC, Ip D. The role of excipients and package components in the photostability of liquid formulations. J Pharm Sci Technol 2003 57(5) 351-368. 

Accurate and quantitative assay results can be obtained [16,17] with MEEKC using internal standards. For example, MEEKC has been used to quantify levels of drug and excipients present in tablet and liquid formulations. 

Excipients such as mannitol can affect small intestinal transit, which in turn can affect the absorption of certain drugs. Oral solutions are rarely likely to fall short of bioequivalence relative to solid oral formulations, although during the development of a ranitidine effervescent oral solution dosage form containing sodium acid pyrophosphate (SAPP), a marked decrease in absorption was observed in the extent of ranitidine absorption from the liquid formulation relative to the conventional oral tablet. The formulation contained 150 mg ranitidine with 1132 mg SAPP together with 1.5 MBq hndium chloride solutions. Small intestinal transit time was decreased to 56% in the presence of the excipient. The rapid small intestinal transit associated with an excipient of a solution dosage form resulted in a decreased extent of ranitidine absorption. " ... 

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