Liquid dosage forms chemical stability

Enhanced mechanical, chemical, and microbiological stability compared to liquid dosage forms... 

Adjustments in pH lo maintain water solubility cun sometimes lead lo chemical stability problems. An example is indomelhacin (HA acid pK ,4.S). which is unstable in alkaline media. Therefore. Ihc preferred oral liquid dosage form is a suspension buffered at pH 4 to 5. Because this is near the drug s pK . only. W f will be in the water-soluble form. There is a medical indication requiring intravenous administration of indomelhacin to premature infants. The intravenous dosage form is the lyophilized (freeze-dried) sodium salt, which is reconstituted just prior lo use. 

Attempts to modify aspirin chemically to either circumvent its potential gastrointestinal intolerance, its poor aqueous solubility (1 300), its poor stability toward hydrolysis (k = 0.002 h-1 which makes liquid dosage forms impossible) and, no doubt Bayer s original patent, has led to the synthesis and evaluation of hundreds of compounds over the years. The modifications involved derivatization of the carboxyl function (such as esters remov-... 

Use of these semisolid and solid approaches can potentially alleviate the chemical stability problems sometimes observed for liquid-Llled formulations, and may eventually offer the possibility of development of a tablet dosage form using conventional equipment. Liquid lipid-based formulations, however, generally afford the greatest enhancement of bioavailability for water-insoluble drugs, as well as affording more rapid development for First-in-Human studies. Any decisions on the best formulation route would have to be evaluated on a case-by-case basis. 

The techniques for predicting the chemical stability of homogeneous drug systems are well defined. " The formulation chemist should consider both the pH-solubility profile and the pH-stability profile when selecting the optimum pH for formulation of the liquid oral dosage form. For example. Figs. 3 and 4 show the... 

A less frequent but nonetheless interesting problem arises in the chemical modification of liquid, or low-melting, active principles in solid prodrugs, suitable for tablet or capsule preparation. Indeed solid dosage forms are still the most widely used for the administration of medicines, as well for patient acceptability and convenience for product stability and ease of manufacture. Their preparation implies that the active principle can itself be handled as a stable solid, an objective that is usually attained by one of the following strategies formation of a salt or a molecular complex, formation of a crystalline covalent derivative, introduction of symmetry. 

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