Dosage Forms for Oral, Ocular, and Nasal Applications
A medicinal agent becomes a medication only after formulation suitable for therapeutic use (i.e., in an appropriate dosage form). The dosage form takes into account the intended mode of use and also ensures ease of handling (e.g., stability, the precision of dosing) by patients and physicians. Pharmaceutical technology is concerned with the design of suitable product formulations and quality control.
Liquid preparations (A) may take the form of solutions, suspensions (a sol or mixture consisting of small water-insoluble solid drug particles dispersed in water), or emulsions (dispersion of minute droplets of a liquid agent or a drug solution in another fluid, e.g., oil in water). Since storage will cause sedimentation of suspensions and separation of emulsions, solutions are generally preferred. In the case of poorly water-soluble substances, the solution is often accomplished by adding ethanol (or other solvents); thus, there are both aqueous and alcoholic solutions. These solutions are made available to patients in specially designed drop bottles, enabling single doses to be measured exactly in terms of a defined number of drops, the size of which depends on the area of the drip opening at the bottle mouth and on the viscosity and surface tension of the solution. The advantage of a drop solution is that the dose, that is, the number of drops, can be precisely adjusted to the patient‘s need. Its disadvantage lies in the difficulty that some patients, disabled by disease or age, will experience in measuring a prescribed number of drops.
When the drugs are dissolved in a larger volume — as in the case of syrups or mixtures — the single dose is measured with a measuring spoon. Dosing may also be done with the aid of a tablespoon or teaspoon (approx. 15 and 5 ml, respectively). However, due to the wide variation in the size of commercially available spoons, dosing will not
be very precise. (Standardized medicinal teaspoons and tablespoons are available.)
Eye drops and nose drops (A) are designed for application to the mucosal surfaces of the eye (conjunctival sac) and nasal cavity, respectively. In order to prolong contact time, nasal drops are formulated as solutions of increased viscosity.
Solid dosage forms include tablets, coated tablets, and capsules (B). Tablets have a disk-like shape, produced by mechanical compression of
the active substance, filler (e.g., lactose, calcium sulfate), binder, and auxiliary material (excipients). The filler provides bulk enough to make the tablet easy to handle and swallow. It is important to consider that the individual dose of many drugs lies in the range of a few milligrams or less. In order to convey the idea of a 10-mg weight, two squares are marked below, the paper mass of each weighing 10 mg. The disintegration of the tablet can be hastened by the use of dried starch, which swells on contact with water, or of NaHCO3, which released
es CO2 gas on contact with gastric acid. Auxiliary materials are important with regard to tablet production, shelf life, palatability, and identifiability (color).
Effervescent tablets (compressed effervescent powders) do not represent a solid dosage form, because they are dissolved in water immediately prior to ingestion and are, thus, actually, liquid preparations.
The coated tablet contains a drug within a core that is covered by a shell, e.g., a wax coating, that serves to (1) protect perishable drugs from decomposing; (2) mask a disagreeable taste or odor; (3) facilitate passage on swallowing; or (4) permit color coding.
Capsules usually consist of an oblong casing — generally made of gelatin
— that contains the drug in powder or granulated form (See. p. 9, C).
In the case of the matrix-type tablet, the drug is embedded in an inert meshwork from which it is released by diffusion upon being moistened. In contrast to solutions, which permit direct absorption of the drug (A, track 3), the use of solid dosage forms initially requires tablets to break up and capsules to open (disintegration) before the drug can be dissolved (dissolution) and pass through the gastrointestinal mucosal lining (absorption). Because disintegration of the tablet and dissolution of the drug take time, absorption will occur mainly in the intestine (A, track 2). In the case of a solution, absorption starts in the stomach (A, track 3).
For acid-labile drugs, a coating of wax or of a cellulose acetate polymer is used to prevent the disintegration of solid dosage forms in the stomach. Accordingly, disintegration and dissolution will take place in the duodenum at normal speed (A, track 1) and drug liberation per se is not retarded.
The liberation of the drug, hence the site and time-course of absorption, are subject to modification by appropriate production methods for matrix-type tablets, coated tablets, and capsules. In the case of the matrix tablet, the drug is incorporated into a lattice from which it can be slowly leached out by gastrointestinal fluids. As the matrix tablet undergoes enteral transit, drug liberation and absorption proceed en route (A, track 4). In the case of coated tablets, coat thickness can be designed such that release and absorption of drug occur either in the proximal (A, track 1) or distal (A, track 5) bowel. Thus, by matching dissolution time with small-bowel transit time, drug release can be timed to occur in the colon.
Drug liberation and, hence, absorption can also be spread out when the drug is presented in the form of a granulate consisting of pellets coated with a waxy film of graded thickness. Depend- ing on film thickness, gradual dissolution occurs during enteral transit, releasing drug at variable rates for absorption. The principle illustrated for a capsule can also be applied to tablets. In this case, either drug pellets coated with films of various thicknesses are compressed into a tablet or the drug is incorporated into a matrix-type tablet. Contrary to timed-release capsules (Span- sules®), slow-release tablets have the advantage of being dividable ad libitum; thus, fractions of the dose contained within the entire tablet may be administered.
This kind of retarded drug release is employed when a rapid rise in the blood level of drug is undesirable, or when absorption is being slowed in order to prolong the action of drugs that have a short sojourn in the body.
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