Solid dispersion can be defined as a cluster of solid creations made up of at least two distinguished components one being a hydrophobic drug and the other a hydrophilic matrix which can take any form depending on the crystalline or amorphous nature of the solids used (see figure 1). In the context of pharmaceuticals, this technology was developed to help improve the solubility and bioavailability of oral drugs. Studies have indicated that a score of patients prefers oral drugs for their simplicity in administration hence they show more compliance in comparison to other types of drugs administered in different ways. However, the functionality of oral drugs is dependent on the level of solubility of the drug molecules and permeability of the gastrointestinal tract. Therefore, the technology of solid dispersion was developed to counteract the disadvantages experienced with drugs characterized with low rates of dissolution.
Figure 1: Solid Dispersion Mechanism
There are three main types of solid dispersion (classified on the basis of their molecular arrangement); Eutectics, Amorphous precipitations in the talline matrix, Solid solutions, Continuous solid solutions, Discontinuous solid solutions, Substitutional solid solutions, interstitial solid solutions, Glass suspension and glass solution (see table 2). These are the main examples used in the technique; however, there are more techniques used depending on the type, or class of drugs used. Moreover, researches based on different fields of drug administration as well as the permeability of membranes have been conducted. The drugs and prescriptions offered in the contemporary pharmaceutical centers have integrated aspects of how appropriate drugs are based on how soluble and permeable they are two different membranes in the gastrointestinal tract. There will be more technological success in the future with technological advances like molecular screening which provides a platform for the testing and analysis of molecules.
There are several advantages that couple solid dispersion technology. This technology enhances the production of particles with reduced particulate sizes. Solid dispersions apply the principle of the particulate nature of solid drugs to enhance their conversion in form of soluble suspensions in the body. Through reducing the particulate size of these solids, a larger surface area is formed, which in turn provides a wider dissolution platform and ultimately improved bioavailability. Additionally, tests and studies of particles produced through solid dispersion have exhibited improved levels of wet-ability. The technique, with respect to this factor, has majored in the evaluation of carriers that influence the dissolution of these particles, as a matter of fact; carriers represent action sites of dissolution. Therefore, improved wet-ability increases the level of interaction between these particles and moisture/water, hence good dissolution potentials.
Also, products from solid dispersion techniques have exhibited increased porosity, a factor that improves carrier potentials with respect to solubility. This, coupled with molecular screening has enabled the infliction of micro pores in polymers and other substances to improve their porosity. As a matter of fact, the more porous a substance is, the more soluble it gets because it increases the number of carrier reaction sites. Therefore, this technology increases the porosity of materials, hence increased permeability, and dissolution. Moreover, the chemical basis that the technology bases its criterion on enables the creation of more amorphous sites in a solid. It’s a logical fact that substances can either be crystalline, amorphous or be composed of varying percentages of both. The crystalline part is close pact with very small or no cleavages in comparison to amorphous sections which has large air spaces that allow the permeability of water and other fluids into the solid morphology. Therefore, increasing the amorphous state of drugs through solid dispersion creates more sites for dissolution, hence increased bioavailability.
On the other hand, solid dispersion has its disadvantages. The activities affect the physical and chemical stability of drugs. Studies in material science and molecular chemistry have shown that modifications done to molecules affect their stability. The molecules of drugs are largely affected when modified to impart wet-ability, porosity and to create amorphous sections in the molecular structure. Additionally, the methods of preparation are very involving and require advanced materials for the study of molecular forms of different types of drugs as well as the equipment to be used in modifying them. Moreover, once it has established that a particular solid dispersion method imparts a certain characteristic to a drug particle, reproducing its physiochemical properties becomes a problem. In fact, there exist other characteristic modifications that happen in the process of solid dispersion that largely affects the original physiochemical properties of the particle.
Also, these modifications yield particles with entirely different molecular formulas and require critical evaluation to determine their composition. This brings about problems in the organization of particles into doses. Furthermore, the manufacturing processes are very expensive given that a large number of drugs are administered orally. Therefore, producing and reproducing these drugs with the desired dissolution levels is a very expensive undertaking. All these limitations provide a challenge at almost each form and level of solid dispersion. However, weighing the different aspects of the technology, calls for more research that would help device new substances and production procedures.
There are wide applications of solid dispersions in the enhancement of the physical properties of an API (Active Pharmaceutical Ingredients). The uses of amorphous solid dispersion techniques in the modification of drugs have helped improve the efficiency of drugs by enhancing the solubility of Active Pharmaceutical Ingredients. As a matter of fact, this technology has necessitated the revision of biopharmaceutical drug classification systems. This is because (as explained in the principle of amorphous solid dispersion), the solubility of drugs is enhanced by modifying the composition of drug molecular structures to have high amorphous sections as compared to crystalline sections. However, there have been cases of stability that comes handy with amorphous solid dispersion techniques. This is because, the modified sections, depending on the mobility of the particles, soon regain their crystalline formations which reduce their permeability and ultimately their dissolution potential.
There exist numerous methods for solid dispersions that solve the misery of integrating the drug and the matrix. Of importance in these methods is the regulation and separation of molecular phases. As a matter of fact, the phases are formed as a result of mobility of particles, where it determines the crystalline and amorphous nature of the resultant composite. Therefore, regulation of phase formation is done through control in mobility of the particles. Fusion or melt method is used when modifying crystalline materials. In this method, the substance is heated together with an appropriate matrix to help in the fusion process. However, the method is limited only to compatible materials within the heating temperature. There are materials that do not mix completely even after they are subjected to certain amounts of heat. Additionally, the process of cooling can result into separation of the materials. Fundamentally, the miscibility of some materials is only as a result of ignition temperatures after which when this heat is removed, the miscibility reduces with the corresponding cooling process.
Additionally, the hot melt extrusion, another method of solid dispersion, employs the principle of fusion but uses force in embedding one layer into the other. An extruder is used in this method which enables the formation of a resultant solid with layers of both materials. The nature and composition of the resultant material with respect to the original materials is determined by the cross-sectional area of the extruder. Different tests are done before the extrusion process is initiated to ensure the right materials are selected. For instance, parameters of solubility for both materials are investigated, and their heat absorption optimums determined to ensure that none of the materials is completely heat (extrusion temperature) sensitive. Furthermore, the solvent method is another technique used in solid dispersion technology. This involves the preparation of a matrix-drug solution after which solvents are harvested from the solution, probably containing both materials in their structure. Finally, the supercritical method involves the use of carbon dioxide as the main matrix. This is both a physical and chemical procedure in which the matrix and drug particles are dissolved in supercritical carbon dioxide. The resultant mixture is then sprayed into a low-pressure vessel which provides conditions for rapid cooling. The particles containing both materials are formed in the process. Essentially, these procedures are chosen after numerous factors have been considered depending on the drug-matrix combination targeted.
The drugs produced through these methods exhibit varying physical structures in both particulate and molecular levels. Fundamentally, the method of preparation determines the physical characteristics of the resultant material. Molecular studies give a comprehensive analysis of the resultant physical characteristics that molecules exhibit when exposed to the divergent chemical and physical conditions. As depicted by the solid dispersion production methods above, the materials are exposed to different types of conditions depending on the method chosen. Logically, the methods are chosen after establishing solubility parameters of all the original materials and factors that affect this aspect. For instance, the conditions that a certain molecule undergoes in fusion method, is entirely different from that which it would experience when exposed to hot extrusion method. The same is a characteristic of the other methods of solid dispersion preparation, hence the physical and structural characteristics of the resultant material.
There are numerous current trends and technological advances that couple the field of pharmaceuticals, there are definitely more sophisticated methods used to produce these materials. As much as the study of molecules helps in the preparation of these materials, the technology is already being used to produce materials for different uses and not necessarily the field of medicine. There are very many examples of solid dispersion products depending on the method used for their preparation. Among others are; Itraconazole, acetylsalicylic acid, diazepam and temazepam, ritonavir, ibuprofen and more others (see table 3)
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