Dosage Forms

1. What is “Pharmaceutics”

Medicines are drug-delivery systems, which very rarely drugs alone but require additives (termed excipients) to make them into dosage forms. The word “pharmaceutics” is used in pharmacy and pharmaceutical science to discuss this conversion from a drug into a medicine. The aim of this subject is to help the administering drugs to arrive in the desired site with a safe, effective, accurate, reproducible, and convenient manner. It encompasses a wide range of stages for designing and manufacturing a new medicine.

2. Principles of formulation design

The formulation of drugs involves information and knowledge from several areas. The physical and chemical properties of drugs and additives have to be taken into account for creating the potential products. It is also necessary to consider the requirements of biopharmaceutics when designing the administration route and formulation, such as the effect on the rate and extent of drug absorption. Finally, the therapeutic consideration of the disease state and patients need to be treated carefully, which will help determine the most suitable type of dosage form, possible routes of administration, and dose frequency. In addition, the package considerations, chemical degradation, and microbial contamination will influence the appropriate quality of final products.

3. Drug delivery design and manufacture

3.1 Solutions

A solution is a homogeneous, molecular, mixture of two or more components. Water is the mostly commonly used solvent because of its lack of toxicity and low cost. Nonaqueous solvents are also used for specific properties in solutions, such as sustained drugs. Solutions can be administrated by many routes, for example, oral, otic, and parenteral. As the drug is already dissolved, hence the drug action can be rapid, which can be used in emergencies. Oral solutions are also beneficial for patients who have difficulties in swallowing (e.g. young children and older people). However, it also has some disadvantages. They are bulky and less stable than dosage forms. In industry, solutions are prepared in large mixing vessels which are thermostatically controlled and achieve a specific temperature.

3.2 Suspensions

A suspension is also a liquid system. Unlike solutions, the solid material (usually the drug) does not dissolve in the liquid medium but remains as solid particles. Solutions are probably one of the most challenging pharmaceutical formulations. Technically, nearly all normal considerations relating to solutions apply equally to suspensions, but with the added issues of particulate behavior. These basic understanding of the interaction between particles in the suspension and between particles and other formulation ingredients can be of great help for successful suspension development. Therefore, it is vital to have a working knowledge of the electrical double layer and the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory of particulate in a suspension.

3.3 Emulsions and creams

An emulsion is a dispersion of two immiscible (or partially miscible) liquids, one of which is distributed uniformly in the form of fine droplets throughout the other. Oil in water (o/w) emulsions contain oil droplets dispersed in water, and water in oil (w/o) emulsions contain water droplets dispersed in oil. Multiple emulsions can also be formed from oil and water by reemulsification of an existing emulsion to form two dispersed phases, such as oil-in-water-in-oil (o/w/o) emulsions.

Creams are white, semisolid preparations, often medicated, intended for external application to the skin and mucous membranes. Structured and semisolid emulsions for dermatological use (lotions and creams) are the largest class of emulsions for medical use.

3.4 Powders and granules

Powders and granules are themselves dosage forms, and also can be filled into sachets for low-potency drugs.

A powder is generally considered to be composed of a collection of solid, loose, dry particles of the same or different chemical compositions having equivalent diameters less than approximately 1000 μm. Two groups of powders are recognized by pharmacopeias –oral powders and topical powders.

It is sometimes necessary for powders to be granulated to prevent segregation of the constituents and improve the flow properties and compaction characteristics of the mix. Granules are preparations containing solid, dry aggregated groups of smaller powder particles, or individual larger particles that may have overall dimensions greater than 1000 μm. There are many types of granulation process: dry granulation (roller compaction) and wet granulation (shear granulators, high speed mixer granulators, fluidized-bed granulation, extrusion-spheronization and spray-drying).

3.5 Tablets

Tablets are normally formed by powder compression. The oral drug delivery is the most route of administrating drugs, and among the oral dosage forms, tablets of various kinds are the most common type in contemporary use. Tablets usually contain active pharmaceutical ingredients (APIs) and excipients. The release of API is a key product attribute and usually controlled by the formulation to achieve immediate release, delayed release or prolonged release. In the manufacturing of tablets, a series of technical problems can arise, such as high weight and dose variation, low mechanical strength, capping of the tablets, adhesion and high frication. Coating, especially film coating, for pharmaceutical tablets, is common place to improve product appearance, make swallowing easier and modify drug release.

References

1.Goodhart, F. W., & Eichman, M. L. (1976). Pharmaceutical sciences—1975: Literature review of pharmaceutics II. Journal of pharmaceutical sciences65(8), 1101-1139.

2. N. Politis, S., Colombo, P., Colombo, G., & M. Rekkas, D. (2017). Design of experiments (DoE) in pharmaceutical development. Drug development and industrial pharmacy43(6), 889-901.

3. Choi, S., Parameswaran, S., & Choi, J. H. (2020). Understanding alcohol aggregates and the water hydrogen bond network towards miscibility in alcohol solutions: graph theoretical analysis. Physical Chemistry Chemical Physics22(30), 17181-17195.

4. Wang, H., & Newby, B. M. Z. (2014). Applicability of the extended Derjaguin–Landau–Verwey–Overbeek theory on the adsorption of bovine serum albumin on solid surfaces. Biointerphases9(4), 041006.

5. Dluska, E., Markowska-Radomska, A., Metera, A., Tudek, B., & Kosicki, K. (2017). Multiple emulsions as effective platforms for controlled anti-cancer drug delivery. Nanomedicine12(18), 2183-2197.

6. Gabbott, I. P., Al Husban, F., & Reynolds, G. K. (2016). The combined effect of wet granulation process parameters and dried granule moisture content on tablet quality attributes. European Journal of Pharmaceutics and Biopharmaceutics106, 70-78.

7. Gabbott, I. P., Al Husban, F., & Reynolds, G. K. (2016). The combined effect of wet granulation process parameters and dried granule moisture content on tablet quality attributes. European Journal of Pharmaceutics and Biopharmaceutics106, 70-78.