Tablet formulation bioavailability

Absorption/Distribution - Absorption of topiramate is rapid, with peak plasma concentrations occurring at approximately 2 hours following a 400 mg oral dose. The relative bioavailability of topiramate from the tablet formulation is approximately 80% compared with a solution. The bioavailability of topiramate is not affected by food. 

The other computation is that of relative bioavailability. This calculation is determined when two products are compared to each other, not to an intravenous standard. This is commonly calculated in the generic drug industry to determine that the generic formulation (e.g., a tablet) is bioequivalent to the original formulation (e.g., another tablet). Thus, bioavailability is not routinely calculated in an individual patient but reserved for product development by a drug manufacturer. However, it is important to have an idea of how formulations or routes of administration differ with respect to bioavailability so as to allow proper dosage adjustment when changing formulations or routes of administration. 

Sutton SC, LeCluyse EL, Engle K, Pipkin JD, Fix JA. Enhanced bioavailability of cefoxitin using palmitoylcarnitine, II. Use of directly compressed tablet formulations in the rat and dog. Pharm Res 1993 10 1516-1520. 

Drug A is a large, peptide-like molecule (MW 700 g/mol) and is highly lipophilic and poorly water soluble. It is a BCS Class II drugs. Its oral bioavailability in capsules and conventional tablet formulations is low, yielding practically undetected blood levels. A novel lipid formulation containing a solvent, a high HLB nonionic surfactant, and a fatty acid were developed with sufLcient oral bioavailability for use in the clinic. 

FIGURE 18.1 Advantages of a solid dispersion formulation, as compared to conventional capsule or tablet formulations, for enhancing dissolution rate, and consequent bioavailability of poorly water-soluble drugs. (From Serajuddin A. T. M. 19991 Pharm ScB8 1058-1066. With permission.)... 

Raoof, A.A., et al. 2004. Oral bioavailability and multiple dose tolerability of an antisense oligonucleotide tablet formulated with sodium caprate. J Pharm Sci 93 1431. 

Formulation design is based on the physical, chemical, and biopharmaceutical properties of a drug substance. A formulation for direct compression is composed of active pharmaceutical ingredients and other inactive ingredients such as fillers, binders, dis-integrants, flow aids, and lubricants. Simplicity is the basis of good formulation design. Minimally, a direct compression tablet formulation must meet requirements for manufacturability, uniformity of dose, physical and chemical stability, appropriate dmg release profiles, and bioavailability. In addition, the formulation must meet many quality standards and special requirements to ensure the efficacy and safety of the product. 

Raoof, A. A., P. Chiu, Z. Ramtoola, I. K. Cumming, C. Teng, S. P. Weinbach, G. E. Hardee, A. A. Levin and R. S. Geary (2004). Oral bioavailability and multiple dose tolerability of an antisense oligonucleotide tablet formulated with sodium caprate. J Pharm Sci 93(6) 1431-9. 

Tribasic calcium phosphate is widely used as a capsule diluent and tablet filler/binder in either direct-compression or wet-granulation processes. The primary bonding mechanism in compaction is plastic deformation. As with dibasic calcium phosphate, a lubricant and a disintegrant should usually be incorporated in capsule or tablet formulations that include tribasic calcium phosphate. In some cases tribasic calcium phosphate has been used as a disintegrant. It is most widely used in vitamin and mineral preparations as a filler and as a binder. It is a source of both calcium and phosphorus, the two main osteogenic minerals for bone health. The bioavailability of the calcium is well known to be improved by the presence of cholecalciferol. Recent research reports that combinations of tribasic calcium phosphate and vitamin D3 are a cost-effective advance in bone fracture prevention. ... 

G. L. Mattock and 1. J. McGilveray. Comparison of bioavailabilities and dissolution characteristics of commercial tablet formulations of suffamethizole. /. Pharm. Sci., 61, 746-9 (1972)... 

Omeprazole, lansoprazole and pantoprazole are highly unstable within the acidic environment of the stomach and lose their activity prior to absorption in the small intestine. The formulations of omeprazole and lansoprazole developed for use in humans utilize an enteric coating to protect the drug as it passes through the stomach. Pantoprazole is available as a delayed-release tablet. The bioavailability of omeprazole, lansoprazole and pantoprazole in humans is 35-60%... 

Softgel formulations, e.g., that of ibuprofen, have a shorter time to peak plasma concentration and greater peak plasma concentration when compared with a marketed tablet formulation. Cyclosporin in softgel form can produce therapeutic levels in blood that are not achievable from tablet form. Similarly, oral hypoglycemic glipizide in softgel form is known to have better bioavailability results when compared with tablet form. 

A tablet formulation should possess the following properties to optimise the technical feasibility, stability and bioavailability of the formulation. 

Compare and contrast tablet formulation and gelatin capsule formulation. What might consequences be to the overall bioavailability of a drug if one formulation dissolves four times faster in the gut than another tablet formulation of the same drug ... 

ABSORPTION, FATE, AND EXCRETION Thiabendazole is absorbed rapidly after oral ingestion and reaches peak plasma concentrations after 1 hour. Most of the drug is excreted in the urine within 24 hours as 5-hydroxythiabendazole, conjugated either as the glucuronide or the sulfate. Tablet formulations of mebendazole are poorly and erratically absorbed, and plasma concentrations are low. The low systemic bioavailability (22%) of mebendazole results from a combination of poor absorption and rapid first-pass hepatic metabolism. Mebendazole is 95% bound to plasma proteins and is extensively metabolized. The major metabolites have lower rates of clearance than does mebendazole and apparently are inactive. Conjugates of mebendazole and its metabolites have been found in bile, but little unchanged mebendazole appears in the urine. 

Chemical stability, disintegration rate, dissolution profile, friability, and hardness are the major stability attributes for the tablet dosage form. An unoptimized tablet formulation may become soft or very hard after storage, with altered dissolution profiles, and as a result, its dissolution profile and bioavailability may not be appropriate. If effervescent products are not properly formulated, manufactured, and packaged, the premature acid-base reaction will cause the product s self-destruction. 

The concentration and the type of disintegrating agent used in a tablet dosage form can greatly influence the dissolution and bioavailability of a therapeutic agent. The dissolution rate is usually increased when the concentration of starch is increased in a tablet formulation. The effect of... 

Figures 9.11 and 9.12 illustrate how changing the concentration of disintegrant (Veegum) in a tolbutamide tablet formulation can greatly alter bioavailability. A comparison of the commercial product (Orinase) with an experimental formulation that was identical in composition and manufacturing method but contained only 50% of the disintegrant (Veegum) showed that the commercial product displayed higher blood concentrations and greater ability to lower blood glucose than the experimental product.

Knupp CA, Milbrath R, Barbhaiya RH. Effect of time of food administration on the bioavailability of didanosine from a chewable tablet formulation. J Clin Pharmacol (1993) 33, 568-73. 

Thomson ABR, Sinclair P, Matisko A, Rosen E, Andersson T, Olofsson B. Influence of food on tile bioavailability of an enteric-coated tablet formulation of omeprazole under repeated dose conditions. Can J Gastroenterol (1997) 11,663-7. 

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