Oral liquids formulation

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). 

Table 11 Antioxidants and Sequestrants Used in Oral Liquid Formulations...

Generally, colors are used to match the flavor or color changes of an oral liquid formulation. Pharmaceutical coloring agents are divided into groups that are soluble in water (dyes) and those that are insoluble in water (pigments). The colors approved for clear liquid preparations are limited to the dyes. 

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). 

Studies in which oral liquid formulations are diluted into simulated gastriid and subsequently into simulated intestinal uid may be useful as amvitro tool for formulation screening (Tong et al.,... 

Table 4. Flow chart of suggested order of solubilization approaches for oral liquid formulations simple to complex .

---