Solid dosage forms oral administration

The majority of oral preparations are solid dosage forms. These include tablets and capsules for administration to small farm animals, pastes for horses, and a variety of prolonged-release products for administration to cattle. The drug in solid dosage form must dissolve before it can be absorbed. The dissolution rate de-... 

Food and Drug Administration. Guide to Inspection of Oral Solid Dosage Forms Pre/Post Approval Issues for Development and Validation. Rockville, MD Office of Compliance, Center for Drugs and Biologies (Jan. 1994). 

In vivo absorption of a chug from an oral solid dosage form into the general circulation after administration is a four-step process ... 

A reduction in particle size results in an increase in the surface area, which facilitates an increase in the dissolution rate and therefore, also, an increase in the rate of absorption. Drugs administered as suspension are generally rapidly absorbed because of the large available surface area of the dispersed solid. For solid dosage forms such as tablets and capsules, decreasing the particle size facilitates dissolution and thus absorption. Figure 6.8 shows the effect of particle size on absorption and resultant blood levels after oral administration of chloramphenicol in rabbits. Peak blood levels occurred much faster with the smaller... 

A medication available only as a solid dosage form, may be prepared as an extemporaneous liquid (e.g., suspension) or it may be modified for oral use, for example, by crushing. As mentioned previously, a sustained-release product should not be crushed or chewed. For a solid, non-sustained-release medication, the product can be crushed and mixed with a small amount of food just prior to administration. Examples of foods that may be used for mixing include applesauce, yogurt, or instant pudding, but the medication should not be added to an entire dish of food or to infant formula, because the infant or child may not eat/drink the entire portion and thus not receive the total amount of medication. 

Most adults consume about 25 g of lactose per day (500 mL of milk) without symptoms.When symptoms appear, they are usually mild and dose-related. The dose of lactose in most pharmaceuticals seldom exceeds 2 g per day. It is unlikely that severe gastrointestinal symptoms can be attributed to the lactose in a conventional oral solid-dosage form, especially in adults who have not previously been diagnosed as severely lactose-intolerant. However, anecdotal reports of drug-induced diarrhea due to lactose intolerance have been made following administration of pharmaceutical preparations containing lactose. 

When drugs are to be administered by the parenteral route, solubilization plays a more important role than in oral administration, as with the latter, a solid dosage form is equally acceptable. Therefore the endotoxin-free types, povidone K12 and povidone K 17 are recommended for parenterals. The molecular weight of both products is low enough (see Section 2.2.6) to allow rapid renal elimination without storage. In many countries in Europe, e.g. Germany and Austria, only such low-molecular povidone types with a K-value of up to 18 are approved for injection (see Section 6.1.3). 

Fig. 2.5 The processes that are interposed between the oral administration of a drug as a solid dosage form and entry of the molecules into the systemic circulation.

Administration of oral solid dosage form of the drug to human subjects during BA/BE study. 

Dosing and Administration. In adults, the initial recommended dose of zonisamide is 100 mg/day. Doses should be titrated by 100 mg daily every 2 weeks to patient response. The dosage range in adults is 100 to 600 mg/day. In children, zonisamide can be initiated at a dose of 2-4 mg/kg per day and titrated to 4-8 mg/kg per day up to a maximum of 12 mg/kg per day. Zonisamide is stable for 48 hours when mixed with water, apple juice, or pudding for patients who have trouble swallowing oral solid dosage forms. 

An alternative to any type of solution is to keep the drug substance in a particulate solid state. This is the normal formulation approach taken for solid dosage forms for oral administration. As long as the rate of dissolution is sufficient to release and dissolve the drug dose in the gastric and intestinal fluids, no problems will arise. The rate of dissolution / of a solid depends mainly on two parameters, namely the solubility C in the aqueous phase and on the specific surface area A of the drug dose that is exposed to the solvent according to the Nemst-Brurmer modified Noyes-Whitney equation ... 

It has been duly observed that the biliary secretion and the enterohepatic recirculation usually account for almost 7 to 30% of the body burden. However, by the oral administration, approximately 50-80% of the drug gets absorbed from the solid dosage forms, but it may be extended upto 90-100% from the hydroalcoholic solutions in capsules. The overall outcome is the enhanced GI motility which gets diminished and hence, the lowered motility enhances the absorption of the drug. 

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