Study of pharmaco-technological properties of solid dispersions of thioctic acid obtained by micronization method

Abstract

Introduction. Thioctic acid is used in the treatment of diseases that are characterized by lack of mitochondrial activity, which is responsible for the formation of free radicals. Widespread use of thioctic acid is due to the chemical structure. The thioctic acid exhibits biological activity in both hydrophilic and hydrophobic environments. Thioctic acid is an enzyme cofactor and a powerful antioxidant, it regulates the transcription of numerous genes, participates in regulation of glucose and lipid metabolism, increases insulin sensitivity, and forms complexes with heavy metals. Thioctic acid has a high pharmacological potential, which is confirmed by the evidence base of clinical trials. An analysis of the literature on the oral use of thioctic acid indicates that solid dosage forms can be used for long-term therapy. This route of administration is limited by factors such as reduced solubility in acidic environments and enzymatic degradation. For this reason, the search for various compositions of auxiliary substances and methods of obtaining drugs is an urgent task of pharmaceutical technology. Material & methods. Objects of study were solid dispersions of thioctic acid (SDTA) on the basis of cellulose derivatives: microcrystalline (MCC), HPMC (hydroxypropyl methylcellulose) and polyvinylpyrrolidone (PVP) as compared to thioctic acid (TA). The samples were made by solid phase method using micronization in a laboratory shredder at a ratio of 1: 1. Pharmacological and technological parameters were determined according to generally accepted methods. Results & discussion. In appearance the resulting mixtures had lemon color, without inclusions and the formation of conglomerates, with homogeneous sized particles According to the pharmaco-technological studies, the samples do not have a satisfactory flowability. The values of the Carr index and the ratio of Hausner make it possible to conclude that there is a large force of cohesion between the particles, a significant aeration of the material. As can be seen from the data presented in the table, micronization in the medium of MCC, PVP and HPMC has led to a change in the density of stacking, which is characteristic of powders with an anisodiametric form of particles, but the strength of the internal friction coefficient has practically not changed, as evidenced by the indicators of the natural slope. The value of porosity suggests a significant degree of the Van der Waals forces action between the particles of the SD. All samples of solid dispersions can be attributed to fragile materials: BW was 5.57 kgf / mm². When stored in a static state, there was a partial agglomeration. The results show that all samples of solid dispersions are well moistened with purified water, as opposed to a sample of tioctic acid. An analysis of the marginal wetting angle indicates that the surfaces of samples of solid dispersions are hydrophilic. According to the microscopic analysis it was established that the influence of external forces has changed the form of the thioctic acid: from the plate with the factor of the form 0,85 to the uncertain form. In samples with microcrystalline cellulose and hydroxypropyl methylcellulose there is a mixture of crushed thioctic acid crystals and carrier. The form factor has dropped to 0.45. The investigation of the dissolution of the obtained solid dispersions showed that the addition of MCC to thioctic acid even reduces the amount of matter passing into the solution, as opposed to solid dispersions with PVP and HPMC (24% and 37% respectively). The difference in the values of dissolution can be due to both the nature of chemical bonds, and the nature of electrostatic attraction, due to the polarity and the emergence of hydrogen bridges. The investigation of the dissolution of the obtained solid dispersions showed that the addition of microcrystalline cellulose to thioctic acid even reduces the amount of matter passing into the solution, as opposed to solid dispersions with PVP and HPMC. The difference in the values of dissolution can be due to both the nature of chemical bonds, and the nature of electrostatic attraction, due to the polarity and the emergence of hydrogen bridges. Conclusion. Thus, the results indicate an increase in the dissolution of thioctic acid in the solid dispersion with PVP in 2.6 times, with HPMC in 1.3 times, which may be the basis for research on the development of solid dosage forms of thioctic acid.