Liquid oral solutions drug solubility

The time to reach the effective blood level of the orally administered drug is too long because of the low dissolution rate, even in case of a complete absorption. There is no aqueous eye drop or injectable solution or other liquid formulation that can be prepared because of the low solubility. 

Liquid formulations account for about 30% of products in the UK market and, because they are easy to swallow, are favoured for paediatric and geriatric use. An aqueous solution is the simplest formulation to produce, but more complex suspensions or emulsion systems will be required if the drug is poorly soluble. Liquid formulations can be administered by all routes and are probably the most versatile systems. Liquids are, however, bulky, difficult to transport and container breakage can result in catastrophic loss. The ultimate aim is to provide the desired dose in a suitable liquid volume which, for oral products, is 5 ml. 

Ritonavir (Norvir Abbott) is a drug for treating patients infected with human immunodeficiency virus-1 (HIV-1). In solid state the compound consists exclusively of one kind of monoclinic crystals. As this form, now called form I, was not sufficiently bioavailable by the oral route, a liquid formulation containing dissolved ritonavir in a hydroalcoholic solution was developed. It gave satisfactory results during the development and early manufacturing phases. However, in 1998, 2 years after the launch, a second form (form II) precipitated during shelf life. The new form is thermodynamically more stable and about 50% less water-soluble than form I. Within weeks-days, this new form was produced in all the production lines and Abbott had to stop the production of ritonavir. Finally, after considerable effort and expense, a new formulation of ritonavir was developed. 

The pharmacist should have anticipated the bio-pharmaceutical consequences of the physico-chemical properties of oxcarbazepine. The drug is classified as a Class II substance for oral application. Logically, lack of adequate solubility is even more evident for the rectal administration as the volume of rectal fluid is limited (see Table 17.1). With an aqueous solubility of approximately 300 mg/L, the solubUity of the substance in the lipophilic base of the suppositories would certainly not be higher than 9.5 mg/mL (being a direct consequence of the value of the log P = 1.5 of oxcarbamazepine). This means that oxcarbazepine is not dissolved in the lipid but dispersed as crystals, which settle from the molten suppository once introduced in the rectal cavity. The amount of rectal liquid is limited and therefore a saturated solution will exist which involves only less than 1 mg dissolved oxcarbamazepine. Low solubility yields a low concentration and hence a low driving force for diffusion to occur. As a consequence, the rate of absorption is relatively low. This slow release may lead to hardly any uptake, due to defecation within several hours after insertion. 

Pharmaceutical suspensions are dispersions of solid particles of an insoluble or sparingly soluble drug in a liquid vehicle, usually water [33, 34]. Several examples of pharmaceutical suspensions are used Oral Suspensions, antibiotic preparations, antiacid and clay suspensions, radioopaque suspensions, barium sulphate suspensions. The vehicle is syrup, sorbitol solution or gum thickener with added artificial sweetener. Topical suspensions (externally applied shake lotion ) such as calamine lotion USP are also formulated as suspensions. Several dermatological preparations are also used in pharmacy. 

The receptor antagonists are water-soluble, neutral-pH, stable compounds that can readily be formulated as solutions ready to inject. Given their stability, they can be given either as bolus or continuous infusion. The liquid formulations can also be administered orally via nasogastric tube. Both methods have been used. Cimetidine, ranitidine, nizatidine, and famotidine are all available as IV solutions, and little difference exists between these drugs in terms of acid control with IV administration. Several studies have reported that continuous infusion gives the best data in terms of control of acid secretion. Unfortunately, relatively few controlled clinical trials have been performed on the effectiveness of many of these solutions. 

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