|
|
 |
|
|
|
|
Amount and type of surface active agents |
|
|
|
|
|
|
|
|
Properties of the capsule wall |
|
|
|
|
|
|
|
|
3. Properties of the dosage form |
|
|
|
|
|
|
|
|
Moisture content |
|
|
|
|
|
|
|
|
Storage contents |
|
|
|
|
|
|
|
|
Age of the drug product |
|
|
|
|
|
|
|
|
Intensity, rate, and type of stirring |
|
|
|
|
|
|
|
|
Fluid dynamics and geometrical factors |
|
|
|
|
|
|
|
|
Concentration gradient between surface and bulk |
|
|
|
|
|
|
|
|
Dissolution fluid composition |
|
|
|
|
|
|
|
|
Temperature of the dissolution fluid |
|
|
|
|
|
|
|
|
1. Pharmaceutical Ingredient (Active Principal) |
|
|
|
|
|
|
|
|
Dissolution of the active ingredient is a prerequisite for absorption. In the case when the dissolution rate is the rate-determining step, i.e., the rate of dissolution is lower than the rate of diffusion to the site of absorption and/or the rate of absorption, then the particle size of the drug may play a very important role in the overall rate of absorption. However, decreasing the particle size in order to increase absorption may only be of importance with compounds of limited solubility (0.1 mg/mL or less). The role of particle size should be considered at solubilities of only 1 mg/mL or less. |
|
|
|
|
|
|
|
|
A larger particle size may be employed if the dissolution rate is not as critical and the effect may be sustained over a longer period of time. Griseofulvin exhibits increased oral absorption following micronization thus making it possible to decrease the dose size. However, the decrease in particle size may be a double-edged sword. As a consequence of increased concentration, chances of toxic effects may also increase. |
|
|
|
|
|
|
|
|
One of the most frequently applied methods to enhance the dissolution rate is to make a salt of the acid or base form of the drug or to prepare coprecipitates. The salt form acts in aqueous solution as a buffer in the diffusion zone and changes its pH value. On precipitation, the prewetted particles of the precipitate are not ionized and, therefore, are more lipid-soluble thus increasing absorption. In the course of formulation, however, the stability of the different salts of the active ingredient in the digestive fluids must be compared. In the case of penicillin salts, the most soluble sodium salt yielded the least bioavailability since it was the most unstable form in the digestive fluid (Fig. 2). Sulfadimethoxine suspension is more bioavailable than its tablet formulation (Fig. 3)another example. |
|
|
|
|
|
|
|
|
The particle size and hence the exposed surface area of the suspended particles for intramuscular or subcutaneous administration is an important factor. The absorption rate of the drug generally increases with increasing surface |
|
|
|
|
|