Study On The Formulation And Preparation Process Of Manidipine Hydrochloride Tablet

The drug solubility is of great significant for its preparation research and it is also an important content of preformulation research. If the drug’s solubility is poor, the concentration of its injection and other liquid pharmaceutical is still lower than the desired concentration for the treatment, although the solution is saturated. With the low concentration, there are no therapeutic effects and the clinical efficacy is poor. Besides the low solubility of solid dosage forms can affect the vivo dissolution and bioavailability.Therefore, the solubilization of insoluble drugs has been concerned by pharmaceutical industries and medical workers. To improve the therapeutic effect of the insoluble drugs, first of all, is to improve the solubility of insoluble drugs. According to the structure and physicochemical properties of the drug, the common methods used to improve the solubilization of drugs are listed as following:ajusting the pH of solution, adding solubilizer or cosolvent, using mixed solvent, preparing water-soluble prodrug, liposomes microspheres or nanoparticles, micro-emulsions, changing the drug crystal form, preparing a solid dispersion, etc.Drug solubility is closely related to the dissolution in solid formulation. The higher solubility, the higher concentration around the particles after disintegration, and the faster dissolution rate, on the contrary, the slower dissolution rate. Therefore, to improve the solubility of the drug in the solid drugs has great significance for improving the dissolution and bioavailability. The methods to increase the solubility of a solid pharmaceutical preparation are changing the drug crystal form and preparing a solid dispersion. There are many ways to increase the dissolution of durgs. According to the characteristics of the insoluble drugs, choose one or several ways to achieve the objective solubilized.Manidipine hydrochloride is a calcium antagonist used to treat hypertension, which is widely used in clinical practice for many years because of its low toxicity, good curative effect and low prices. However, the ordinary preparations of Manidipine hydrochloride have low solubility and dissolution, which can impact the efficacy greatly. In this paper, hydrophilic gel technology solves the problem of manidipine hydrophobicity, increases the solubility in water, improves the dissolution, and achieves the same dissolution profile as the RLD. It solves the problems of low dissolution lasting for years.1. Prescription and process researches of Manidipine hydrochloride tabletsManidipine hydrochloride belongs to BCS class2(low solubility-High permeability drugs), which has strong hydrophobicity and small density, and easy to float in the dissolution medium. For these characteristics, micronized, solubilization techniques solid dispersion technique, the hydrophilic gel matrix for formulation and process technology research were used in this paper. Formulation and process were determined by uniform and orthogonal design. Three batches of pilot samples were prepared to inspect the stability of formulation and technology of manidipine hydrochloride tablet, and the results show that the hydrophilic gel matrix technology could improve the hydrophobicity and the tablet dissolution meet the quality standards. The simple process was suitable for industrial production and three batches of pilot samples dissolution are similar to RLD.2. Quality specification study of manidipine hydrochloride tabletsThe tablets are identified by UV-visible spectrophotometry and high performance liquid chromatography (HPLC) on the basis of the structural characteristics of manidipine hydrochloride; The dissolution of tablets is detected by HPLC and the methods for dissolution detection is determined by methodological studies, such as membrane selection, linear relationship, precision, stability and recovery testing, etc; The dissolution profiles compared with the RLD show that the dissolution of pilot samples in vitro is the same as RLD; The related substances are studied by HPLC. The starting materials, intermediates and degradation products and other specific impurities are confirmed with the analysis of the synthesis routes and the degradation products. Destructive testing and the positioning and separating of each impurity tests prove that the proposed chromatographic conditions could efficiently detect the impurities, and robustness tests proved the chromatographic conditions has excellent robustness. The related substances method was finally detected by the methodology experiments of oxidation impurity and0.2%self-reference methodology experiments. The assay test method is determined by the linear relationship test, precision test, stability test and recovery test under the chromatographic conditions of the related substances. The vitro dissolution, related substances, assay and the other indicators of the three batches of pilot samples meet the specification, and there was no significant differences compared with the RLD.3. Stability studiest of manidipine hydrochloride tabletsThe accelerated and long-term experiments are conducted according to 《Guiding principles for stabilization of raw material and drug》(Chinese Pharmacopoeia2010Volume Ⅱ Appendix X IX C). The appearance and identification test of three batches pilot sample meet the specification after accelerated studies for6months and Long term studies for24months. The dissolution, related substances and assay are no significant difference compared with the result of samples of the0day. The results showed that the quality of manidipine hydrochloride tablets is stable.Conclusion:The experimental results indicated that the formulation and process of Manidipine hydrochloride tablets prepared by hydrophilic gel technology are reasonable and practicable, its process is stable and the quality can be controlled.