One of the most promising directions for optimizing the biopharmaceutical properties of drugs is the method of obtaining solid dispersion systems (SDS). SDS are bi- or multi-component systems consisting of an active pharmaceutical ingredient (API) and a carrier, and represent a highly dispersed solid phase of the API or solid solutions that form complexes with the carrier material.
The low solubility of many APIs in the aqueous environment has become one of the main challenges of pharmaceutical science, especially when it comes to oral solid dosage forms.
The solubility of API in the aqueous environment determines the possibility of effective introduction of the drug into the human body, and the solubility in non-polar solvents - the ability to pass through the lipid barrier of biological membranes. Thus, the factor of solubility in polar and non-polar environments affects the processes of introduction, subsequent transmembrane transfer of API and its overall therapeutic effectiveness [1].
Therefore, increasing the oral bioavailability of poorly water-soluble APIs is an urgent task in the development of original and generic drugs.
Currently, polymer-based SDS are considered one of the main achievements in the field of overcoming the problems of limited solubility and permeability of API.
The purpose of this review is to analyze current approaches to the creation and commercialization of solid dispersion systems and to assess the prospects for the pharmaceutical industry.
In addition to increasing API dissolution, the use of SDS allows solving a number of other applied problems in the creation of drugs:
- release modification;
- increase in chemical and physical stability;
- required pharmaco-technological properties;
- elimination of undesirable properties (side reactions, unpleasant organoleptic properties);
- the ability to bypass patent restrictions on formulation, particle size or polymorphic modifications to create generic drugs [2].
SDS can be defined as a system consisting of a hydrophobic or sparingly soluble API dispersed in a hydrophilic carrier medium. The role of the carrier is usually performed by pharmaceutically acceptable water-soluble or hydrophilic polymers (polyethylene glycol, polyvinylpyrrolidone, cellulose derivatives, and others). Optionally, surfactants can be included in these systems [3].
Industrial technologies on the basis of which solid dispersed systems can be obtained - hot melt extrusion, dissolution and solvent removal, solvent removal by spray drying, production of systems in a fluidized bed, production of systems by high shear granulation, high energy mixing (KinetiSol®).
Currently, there are more than 30 drugs using SDS based on pharmaceutically acceptable polymers, which are available on the market and are approved by the US Food and Drug Administration (FDA). Although the first drugs using SDS were commercialized in the 70s of the last century, by 2010 only about 10 such drugs were known, and in recent years there has been a significant increase in the number of such products [4]. In view of the significant scientific capacity and complexity in terms of technological, physico-chemical and regulatory aspects of implementation, the lion's share of commercialized SDS is represented by the flagship companies of the pharmaceutical market (Pfizer, Merck, Janssen, Bayer, Novartis), which definitely confirms the prospects for the development of this direction [5].
Use of SDS is relevant for pharmaceutical science and practice. The implementation of such an approach in the creation of drugs provides opportunities for improving their biopharmaceutical properties and significantly expands opportunities and competitiveness.