A study of the influence of solvents on crystallographic characteristics of local anesthetics

Abstract

Introduction. Esters of para-aminobenzoic acid (PABA) – benzocaine and substituted amides – lidocaine and trimecaine are used in suppositories as substances with anesthetics effect. When benzocaine is used to reduce pain the effect develops for 1 minute after applying of rectal dosage forms and lasts for 20-30 minutes. The maximum effect of lidocaine is manifested within 15-30 minutes after using the medications. Trimecaine is absorbed rapidly and has a period of action of 60 minutes, but in the presence of inflammation, it is possible to decrease the anesthetic activity. The above local anesthetics have a low toxicity, which is an essential aspect in the formation of medications. Material & methods. The study objects were benzocaine (Changzhou Sunlight Pharmaceutical Co., Ltd., China), lidocaine hydrochloride (Societa Italiana Medicinali Scandicci srl (S.I.M.S. srl), Italy) and trimecaine hydrochloride (Interpharma Praha, a.s., Czech Republic). Definition of crystallographic characteristics in a solvent was carried out a microscopic method using a Konus Academi Microscope of Italian production with a DLT-Cam Basic 2MP camera. DLTCamViewer ™ software was used to visualize images for definition of the shape and size of particles over time. The solvents used to have different dielectric conductivity: (water - 78.3, propylene glycol - 32.0, ethanol - 25.2, macrogol -400 - 14.1, witepsol - 2.5). The crystallographic characteristics of the substance established on value of the Fere's diameter (Df) and shape factor (k). The statistical processing of result carried out in accordance with the requirements of the SPhU using the software Microsoft Excel 2007. Results of the study are showing that the form and size of benzocaine, lidocaine, trimecaine significantly differ from each other. Benzocaine has volumetric particles, which are close to the rectangular shape, with a linear size of 0.5 to 7 μm in maximum measurements, k = 0.2 - 0.5 μm, Df = 2 μm, with an uneven surface and numerous debris. Lidocaine has particles that are capable of agglomeration, linear size 0.1-1.2 μm, k = 0.4, Df = 0.6 μm. In the sample of trimecaine there is a uniform distribution of transparent particles that are close to the rectangular shape, capable of agglomeration, with a linear size of 0.05-1 μm, k=0,7, Df = 0,9 μm. The resulting data are confirmed by the results of the dispersion analysis of the particle size distribution, shown that to the law of normal distribution is obeyed in a sample of trimecaine. The differential curve of this substance has one maximum similar to a fraction with a particle size of 0.1-0.2 μm. In other samples, the height of the maximum are reducing, the curve becomes more stretched, that indicating about their polydispersity. Lidocaine has the largest area between the differential curve and x-line (Fig. 2), which indicates that it has almost equally particle ratio of all fractions. In a sample of benzocaine, a fraction with size of 0.5 μm is prevailing. The obtained results show the dependence of the samples of dissolution degree on the index of dielectric conductivity. Thus, the solubility of the witepsol decreases with increasing dielectric conductivity and reaches maximum at 2.5. The property of the dissolution of lidocaine and trimecaine is different - the solubility increases with increasing dielectric conductivity, the maximu m dissolution at 78.3.Taking into account the obtained data, we can conclude about advisability of benzocaine introduction into suppositories in the form of a solution in the environment with dielectric permittivity to 2.5 and for lidocaine and trimecaine in the range 25-78. The substance can be introduced by suspension in the environment with different dielectric permittivity.