Particle science and calculations

[Extract] This chaper includes important topics of pharmaceutics asociated with powdered drugs, including solid-state properties, particle size anaylsis and reduction, mixing, powder flow, granulation, drying, and coating and multiparticulates. Since most active and inactive pharmaceutical ingredients occur in the solid state as amorphous powders or as crystals, there are often many formulation challenges (e.g. polymorphism, hydrate formation) that must be overcome in order to design dosage forms suitable for manufacture that guarantee their satisfactory performance in patients. As polymorphism may have an effect on the bioavailability of drugs, especially those with low aqueous solubility, it is important not only for pharmaceutical manufacturers but also for pharmacists and pharmacy students to be aware of factors that may cause a polymorphic change. Although this is largely the domain of the pharmaceutical scientist in the industry, there are certain conditions, such as high humidity during storage, that might bring about a change in the form of the drug and potentially its therapeutic efficacy. This chapter introduces solid-state properties, which due to the fact that most drugs and excipients exist as solids, are of considerable pharmaceutical importance. A description follows of some of the macroscopic properties that are important in dosage form design, including particle size, analysis and reduction. Particle size control is an important aspect of dosage form design, beginning with the formulation and manufacturing stages, right through to the efficacy of the drug product after administration to the patient. Particle size reduction is often required to facilitate efficient processsing of drugs that need to be mixed or to ensure the production of an aestheically pleasing suspenion. Since very fews drug products contain only one ingredient, mixing is reqauired during manufacture to ensure the even distribution of the active pharmaceutical ingredient (API)through the dosage forms. Effective mixing also results in a good appearance of the drug product and is requiered so that the API is released at the correct rate at the site of action. Mixing is required during the production of solid dosage forms, ranging from tablets through to dry powder inhalers. Since drug powders are used primarily to produce tablets and capsules, the flowability of these powders is of significance in the prouction of pharmaceutical dosage forms, after mixing, granulation involving the formation of large multiparticles is undertaken to ensure even disribution of each ingredient throuhout the mix. The drying process is often the last stage of manufacture before packaging and is important to ensure that the residual moisture is low enough so that the powder flows and the drug product does not deteriorate on storage. Coating tablets and capsules is underaken for a number of reasons, but primarily to protect the API from the environment. Coating of pellets and beads, referrered to as multiparticualtes, is undertaken to produce drug products with an extended release, because this requires less frequent dosing by the patient, improved adherence is noted. The final section of this test is dedicaed to pharmaceutical calulations, a critical role for the pharmacist in all areas of practice, whether in dispensing or manufacturing