Author: Morné Fouché, Jan Steenekamp, Hannlie Hamman , Josias Hamman
many active pharmaceutical ingredients (APIs) exhibit poor solubility and low dissolution rates in aqueous environments such as the luminal fluids of the gastrointestinal tract, oral bioavailability of these compounds is usually very low as a result of their poor solubility properties, formulation strategies to improve their aqueous solubility and dissolution rates, , or specialized dosage forms can be formulated that improve dissolution rate through various mechanisms, selected excipients (e.g., alkalinizing agents, surfactants and sugars), specialized dosage forms such as self-emulsifying delivery systems and formulation techniques such as inclusion complexes and solid dispersions, drug solubility and bioavailability enhancement, specialized dosage forms such as self-emulsifying delivery systems and formulation techniques such as inclusion complexes and solid dispersions, pharmacologically active compounds or drugs (also referred to as active pharmaceutical ingredients; APIs) are usually not administered to patients on their own as single compounds, but are formulated into carefully designed dosage forms, Pharmaceutical dosage forms provide a platform for repeatable accurate dosing, quality, efficacy, safety, stability as well as high patient acceptance and compliance, dosage forms were made by simply adding pharmacologically inert substances (also referred to as excipients) to the API to make up the required volume of an acceptable dosing unit, selection and production of excipients that fulfil specific functions, beyond just making up volume, such as assisting in production of the dosage form and optimizing drug delivery from novel dosage forms, stability of the API, dose uniformity, effective delivery of the API to the systemic circulation after administration as well as acceptable organoleptic properties, excipients are 90% of the total mass/volume of medicinal products, different classes of pharmaceutical excipients have different requirements in terms of safety evaluation, updates on regulatory requirements for pharmaceutical excipients are continuously introduced worldwide to ensure the safety of patients, multifunctional excipients refer to excipients (which can be co-processed for example) that fulfil multiple roles in a dosage form or drug delivery system, for example a direct-compressible filler material that also functions as a binder and/or disintegrant, high functionality excipients refers to a single excipient that provides additional functions to innovative drug delivery systems to improve the overall performance of the product with significant economic benefits, high functionality excipient is one that can provide better flow, act as a disintegrant and simultaneously allow a higher drug loading in the dosage form due to its high compressibility, 40% of current medication dispensed to patients in pharmacies exhibit relatively poor aqueous solubility properties, 90% of newly discovered therapeutic compounds in the development phase exhibit poor aqueous solubility, future research regarding the identification of solubility-enhancing excipients is of cardinal importance, functional excipients are needed to assist in overcoming their poor physico-chemical properties, Specialty excipients are used to produce dosage forms that can reduce the number of doses by modifying the rate of drug release or improve drug delivery by targeting drug release in a specific region in the gastrointestinal tract where drug absorption is the highest. Functional excipients are also used to re-formulate existing drugs in order to produce more effective products that are more cost-effective, a drug that exhibits an aqueous solubility lower than 0.1 mg per mL is likely to experience limited bioavailability, and its rate of absorption will be governed by the dissolution rate, Physico-chemical techniques that have been employed to improve the solubility of these drugs include formation of pro-drugs, formation of salts, co-precipitation, solvent evaporation and size reduction (or micronization), Formulation strategies that have been investigated for the same purpose include melt extrusion/granulation, formation of solid dispersions and formation of inclusion complexes. Furthermore, excipients such as surfactants, polymers, super-disintegrants and multifunctional fillers have been included in dosage forms to increase the apparent solubility of drugs, term complex formation or complexation refers to the binding of two or more individual molecules to form a combined chemical product, which act as a single chemical unit, dosage forms include conventional immediate release tablets, orally disintegrating tablets, effervescent tablets, and modified release dosage forms including slow release or sustained release drug delivery system, excipients that can increase an APIs solubility and dissolution rate include cyclodextrins, disintegrants, pH-adjusting excipients, natural polymers, surfactants, co-surfactants, oils/lipids and sugars, special interest to determine the clinical significance or value of formulation approaches on drug bioavailability and if they could result in decreasing the dose needed to reach effective blood plasma levels, Identifying the correct formulation method and using the suitable excipient in relation to the API may result in efficient pharmacological treatment by means of administrating a lower dose, which may have a significant cost implication.
