The freeze-drying process has been widely used in the preparation of pharmaceutical preparations. Usually, water is the only solvent, but sometimes the organic solvent remaining in the extraction and crystallization process may be carried into the final lyophilized solution, which will lead to some new changes, including a small amount of organic The lyophilization process of the solvent solution has attracted attention and has been studied intensively. The tert-butanol-water co-solvent is the most common one, and the process of freeze-drying with it as a solvent can be used for preparation of various preparations, and has various advantages.
Since tert-butyl alcohol has multiple advantages as a lyophilized agent, it has been widely used in preparations, and pure tert-butanol can be used as a solvent alone to dissolve a water-insoluble drug or a drug having poor stability in water, and freeze-dried. More research at home and abroad is that t-butanol forms a cosolvent system with water for freeze-drying, and its application in the field of pharmacy has many aspects.
â– Preparation of solid preparations has obvious advantages
The poorly water-soluble drug is dissolved in tert-butanol, the water-soluble substance is dissolved in water, and the two are mixed in an appropriate ratio to obtain a clear cosolvent which can dissolve the water-soluble and fat-soluble substance together, and the solution can be further freeze-dried. A solid dispersion is obtained. There are a number of benefits to preparing a medicament using this process.
Accelerate the sublimation rate of the drug. It is found that the solution of the gentamicin-dissolved t-butanol is mixed with the aqueous lactose solution in a suitable ratio to form a co-solvent, and then freeze-dried. The freeze-drying period can be shortened from 39 hours to 28 hours, and the obtained lyophilized solution is obtained. The product remains porous.
Improve the stability of the drug Prostaglandin E is a poorly stable drug. The drug and lactose are co-dissolved with a volume fraction of 20% t-butanol-water cosolvent, and a freeze-dried powder needle is obtained after lyophilization. At present, prostaglandin E aseptic powder preparations produced by this freeze-drying process have been marketed abroad.
Solubilizing the poorly soluble drug Aldipine is an anticancer active substance extracted from marine organisms with a relative molecular mass of 1109 and is almost insoluble in water. The researchers explored a new method of solubilization: the drug was first dissolved in t-butanol, and then formed into a clear co-solvent in a ratio of 4:6 by volume of lactose aqueous solution, and lyophilized to obtain a stable lyophilizate. The polyoxyethylene castor oil-ethanol-water cosolvent system was used for reconstitution before use, and diluted with physiological saline and then administered by Injection.
Simplified Process for Preparing Solid Dispersions Recently, researchers have co-dissolved fat-soluble drugs together with water-soluble oligosaccharides in a t-butanol-water cosolvent system and lyophilized to form a solid dispersion. By this method, the fat-soluble drug can be dispersed in some amorphous materials with higher glass transition temperature, so that the drug remains in an amorphous state, which can significantly improve the dissolution rate of the drug and the solubility of the drug. This process can avoid the destruction of the drug with poor thermal stability by the solid preparation of the solid dispersion by the melt method, and can avoid the use of the more toxic solvent such as chloroform or dichloromethane when preparing the solid dispersion by the solvent method.
Promoting drug crystallization The tert-butanol-water cosolvent system produces a solid dispersion that maintains the drug in an amorphous state. On the other hand, tert-butanol can also be used to promote the crystallization of difficult crystalline drugs. This is because the addition of t-butanol changes the crystal state of water, which in turn changes the crystalline state of the drug dissolved in water. Studies on the antibiotic cefotaxime sodium have found that the addition of a small amount of t-butanol allows needle-like crystallization of a drug that is difficult to crystallize. Sodium fosfomycin is a substance that is difficult to freeze. Because the binding force between the drug and water is strong, the freezing point of the formed hydrate drops sharply to around 50 °C. It is difficult for ordinary lyophilizers to freeze it, and at the same time, very low temperature. The lyophilization cycle of the drug is greatly extended. When t-butanol is added, the binding point of t-butanol and water is strong, so that the freezing point of the co-solvent system is increased, and the sublimation speed is greatly improved.
â– Preparation of various dispersion systems
The liposome is prepared by dissolving the phospholipid with tert-butyl alcohol as a solvent, and lyophilized to obtain a loosely-structured phospholipid solid, which can be rapidly hydrated to form a liposome by adding water. This method is similar to the film dispersion method, and can produce micron-sized multi-chamber liposomes with larger particle diameters. This liposome preparation process has been applied to trial and scale production.
Recently, researchers at Shenyang Pharmaceutical University invented a new liposome preparation process, which is to dissolve soybean phospholipid with low phase transition temperature in tert-butanol, and further mix with sucrose aqueous solution in an appropriate ratio to obtain a clear solution and freeze-dry. A solid dispersion is obtained, and water is added to obtain a small single-chamber liposome having a uniform particle size. This process solves the problem of poor liposome stability and establishes a model for the formation of small single-chamber liposomes. During the lyophilization process, the phosphotide tert-butanol solution precipitates crystals first. The formation of this crystal is limited by the viscosity of the sugar solution, and only a small particle size can be formed. At the same time, in the phase separation process of precipitation crystallization, phospholipid acts as a surfactant, adsorbing on the interface of the two phases, reducing the surface tension, that is, the phospholipid-coated tert-butanol is dispersed in the sugar matrix, eventually forming a similar The state of the emulsion. The phospholipid adsorbed at the interface of the two phases sublimes with t-butanol during lyophilization to form a bilayered segment of the phospholipid. Since the bimolecular fragment is small enough, a small single-chamber liposome is formed after hydration.
The researchers designed another process for saturated phospholipids with a high phase transition temperature, which is dissolved in tert-butanol, injected into water at an experimental temperature greater than the phase transition temperature, forming liposomes, and then lyophilized to obtain lyophilization. Liposomes. This method can shorten the freeze-drying cycle.
Studies have shown that the saturated phospholipid DMPC-DMPG (molar ratio of 7:3) and the anthracycline anticancer drug Annamycin are dissolved in the tert-butanol-dimethyl sulfoxide-water cosolvent system at a mass ratio of 50:1. The surfactant Tween-80 is added and freeze-dried to form a lyophilized powder, and submicron-sized liposomes can also be obtained after hydration.
Preparation of some nonionic surfactants other than nonionic surfactant vesicle phospholipids, can also be co-dissolved in a t-butanol-water system with a water-soluble medium, freeze-dried to obtain a lyophilized dispersion, and hydrated to obtain a nonionic surfactant. Agent vesicles.
Preparation of polymer micelles Some polymer copolymers can form micelles with fat-soluble drugs, increasing the solubility of drugs in water. The usual practice is to co-dissolve the polymer copolymer and the drug in water. This method causes a decrease in drug loading for many poorly water-soluble drugs, and is often required due to poor water solubility of the polymer material itself. The two were dissolved together in an organic solvent and then dialyzed off with water. Still another method is to form an oil-in-water emulsion followed by removal of the organic solvent. These methods are complex and uneconomical. Recently, a t-butanol-water system has been introduced into the preparation process of high polymer micelles, and polymer micelles of paclitaxel and docetaxel have been prepared, and good results have been obtained. The method comprises the steps of: cosolving a drug with a polymer to prepare a clear solution, and adding a hydrated solid dispersion to obtain a micelle of less than 100 nm. The process is simple, convenient, and effective, and the tert-butanol-water co-solvent can also be recycled, which increases the feasibility of mass production.
â– Improve the formulation route
Since the tert-butanol-water cosolvent system can dissolve the water soluble and fat soluble materials together, the solvent can be removed after lyophilization. Therefore, this method can be used to improve the preparation process of many preparations.
Oral administration of protein peptides has been a hot and difficult point in current research. The tert-butanol-water cosolvent system provides a new means of drug delivery for the water-soluble protein-polypeptide to be dissolved in an oil solution. The researchers used a t-butanol-water cosolvent system, freeze-dried to prepare a protein-polypeptide-containing phospholipid dispersion, and dissolved the lyophilized dispersion in an oil solution to form a water-soluble protein-polypeptide-reverse gummed oil. Solution. In order to solve the solubility of poorly soluble drugs in water, a cyclodextrin inclusion technique is usually employed. Conventional freeze-drying uses ethanol as a solvent to dissolve poorly soluble drugs. Due to the limited solubility of ethanol, it is usually necessary to use more solvents, and the cosolvent system containing ethanol is not easy to freeze, and the freeze-drying effect is not good. Therefore, the researchers dissolved the drug and cyclodextrin in a t-butanol-water cosolvent system and freeze-dried to form a clathrate. Since tert-butyl alcohol has a stronger ability to dissolve poorly soluble drugs than ethanol, and freezes completely and rapidly, this method provides a convenient new process for preparing cyclodextrin inclusion complexes.
Glimepiride Tablet,Glimepiride Apis,Type Ii Diabetes Tablet,Control Blood Sugar Tablet
SHANDONG XINHUA PHARMACEUTICAL Co., Ltd. , https://www.sdxinhuapharm.com