Bioavailability drug formulation

The critical void in pediatric drug therapy now lies in effective drug-delivery systems. Some inroads have been made in the manufacturing of pediatric dosing systems, particularly OTC preparations. There needs to be a redirection of the focus in nonparenteral drug formulations towards pediatric dosage forms with proven stability and bioavailability that can be easily and accurately administered to infants and children. 

A. D. Waston, Bioavailability and bioinequivalence of drug formulations in small animals, J. Vet. Pharmacol. Ther, 15, 151 (1992). 

Schrader E, Schwankl W, Sieder C, Christoffel V. Comparison of the bioavailability of beta-aescin after single oral administration of two different drug formulations containing an extract of horse-chestnut seeds. Pharmazie 1995 50 623-627. 

Overdosage and underdosage relative to the prescribed dosage—both aspects of failure of compliance—can frequently be detected by concentration measurements when gross deviations from expected values are obtained. If compliance is found to be adequate, absorption abnormalities in the small bowel may be the cause of abnormally low concentrations. Variations in the extent of bioavailability are rarely caused by irregularities in the manufacture of the particular drug formulation. More commonly, variations in bioavailability are due to metabolism during absorption. 

Oxolinic acid is quickly absorbed after oral administration, but its absorption is variable and dependent on animal species, drug formulation, diet, and disease status. After an oral dose of 10 mg/kg bw, bioavailability was approximately 82% in healthy chickens, but around 100% in diseased chickens. Oral bioavailability was also higher in swine and calves, but lower in fin fish and Atlantic salmon. The bioavailability of oxolinic acid given as medicated feed at a single dose 9-26 mg/kg bw to Atlantic salmon kept in seawater at 7.5-9 C was estimated to be 20-21% (188, 189). 

Many drugs can now be delivered rectally instead of by parenteral injection (intravenous route) or oral administration. Generally, the rectal delivery route is particularly suitable for pediatric and elderly patients who experience difficulty ingesting medication or who are unconscious. However, rectal bioavailabilities tend to be lower than the corresponding values of oral administration. The nature of the drug formulation has been shown to be an essential determinant of the rectal absorption profiles. The development of novel absorption enhancers with potential efficacy without mucosal irritation (low toxicity) is very important. The delivery of peptide and protein drugs by the rectal route is currently being explored and seems to be feasible. 

Bioadhesive formulations and microsphere delivery systems in particular have attracted much attention. As drug formulations are usually rapidly removed from the site of deposition by the mucociliary clearance, increasing the retention time of drug in the nasal cavity via bioadhesion can increase bioavailability [28], Bioadhesion may be defined as the ability of a material (synthetic or biological) to adhere to a biological tissue for an extended period of time. When applied to a mucous membrane, a bioadhesive polymer may adhere primarily to the mucus layer or epithelial cell surface in a phenomenon known as mucoadhesion [29,30]. The bioadhesive properties of a wide range of materials have been evaluated over the last decade. 

R. H. Muller, C. Jacobs, and 0. Kayser. DissoCubes—A novel formulation for poorly soluble and poorly bioavailable drugs, in Michael J. Rathbone, Jonathan Hadgraft, and Machael S. Roberts (eds.), Drugs and the Pharmaceutical Sciences, Vol. 126 Modified-Release Drug Delivery Technology. New York Marcel Dekker, 2003, pp. 139-149. 

To assess the changes in bioavailability caused by changes in drug formulation. 

Factors that can affect bioavailability include metabolism (to be discussed in more detail in Chapter 3), lipid solubility of the drug, chemical stability of the drug (e.g., penicillin G is unstable at gastric pFI), and the nature of the drug formulation (i.e., particle size, salt form, presence of inert binders, etc.). 

Understand the drug-, formulation-, and patient-related factors influencing oral drug bioavailability,... 

Given the considerable challenge of ocular drug delivery, i.e. short contact time and low drug bioavailability, mucoadhesives are attractive excipients in ophthalmic drug formulations. The presence of mucin in the eye allows bioadhesive polymers to thicken the tear film in the front of eye. 

Bioavailability studies quantify rate and extent of absorption. They compare the efficiency of the disposition of several drug formulations, e.g. immediate-release vs. extended-release or capsule vs. tablet or tablet A vs. tablet B etc., or they compare the disposition of different routes of administration, e.g. oral vs. subcutaneous or oral vs. intravenous. According to the definition, a comparison to the intravenous bolus injection yields the absolute bioavailability. 

Many steps are involved in the successful design of an ocular drug formulation.The first is selection of an appropriate drug molecule that maximizes therapeutic benefit and bioavailability while minimizing toxicity. A formulation must then be developed to include a vehicle, a preservative, and a buffer. 

The mechanism of absorption must always be evaluated when a sustained-release dosage form is considered. A drug that is passively absorbed throughout the GI tracts is an ideal candidate for sustained release. Drugs such as riboflavin, folic acid, aminopenicillins, amino-p-lactams and nucleoside analogs, which have windows of absorption due to site-specific and/or active transport processes, may have incomplete bioavailability when formulated in oral, sustained-release dosage forms. 

---