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Three Ways to Improve the Bioavailability of Poorly Soluble Drugs

2021-01-28
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Due to the difference in particle size or added excipients of poorly soluble drugs, the oral dose will be the same, but the efficacy will be very different. In the development of solid preparations, increasing the solubility of poorly soluble drugs and improving the bioavailability of drugs, thereby promoting the absorption of drugs in the human body, and improving the clinical effects of drugs are an important part of pharmaceutical research. To improve the solubility of poorly soluble drugs and increase the bioavailability, more common tasks can be gradually carried out from the three links of raw material micronization, addition of surfactants, and solid dispersion.

Poorly Soluble Drugs

1. Micronization of raw materials

Since the dissolution rate of a solid is directly proportional to the contact surface area of ​​its dissolution medium, reducing the particle size to increase the surface area is currently a common method for increasing the dissolution of poorly soluble drugs in the gastrointestinal tract and improving the bioavailability. In the research and development of solid preparations, the crushing of the bulk drug is the first and crucial step in the preparation of tablets. The micronization of bulk drugs is one of the effective means to solve the solubility of poorly soluble drugs. Compared with large particles, the dissolution rate of the micronized drugs is faster, the solubility is higher, the adhesion is stronger, and it can be dispersed at a faster rate Into the blood.

For example, a researcher has established a method for the dissolution test of cefdinir granules, and investigated the dissolution of cefdinir granules before and after the micronization of the API [1]. The researchers used the second method of dissolution test-paddle method, and measured by ultraviolet spectrophotometry, respectively, under three dissolution media of hydrochloric acid solution, pure water, and pH7.2 phosphate buffer at a speed of 50r/min and a volume of 900mL. Compare the dissolution behavior of cefdinir granules before and after the micronization of the API. The results of the study found that this method can be used for the determination of the dissolution of cefdinir granules, and experiments have shown that the micronization technology can improve the dissolution of poorly soluble drugs.

In the research and development of solid preparations, dissolution test is one of the important control items of drug quality, and it is also an effective method to evaluate the formulation and production process. It can evaluate the bioavailability and uniformity of solid preparations. Medicilon has the equipment and instruments commonly used in preparation process research and quality research such as tablets, injections, capsules, granules, ointments, creams, sprays, gels, syrups, tinctures, oral liquid preparations, and The GMP pilot plant for oral solid preparations also has the ability to develop new technologies such as sustained and controlled release preparations, nano preparations, and fat emulsions.

2. Increase cosolvent or surfactant

The use of cosolvents and poorly soluble drugs to form complexes, molecular complexes, etc. can achieve the solubilization effect of the cosolvent, and a suitable cosolvent can make the drug exert a better effect. If iodine is hardly soluble in water, potassium iodide can be used as a cosolvent to form a complex with it.

Surfactants are solubilizers, which increase the amount of dissolved drugs by forming micelles. In the development of solid preparations, surfactants often act as wetting agents in solid preparations, and surfactants are rarely added to solid preparations for the purpose of solubilization. Because the amount of surfactant that can be added is very limited, generally only a few milligrams, after the patient takes it, the surfactant is greatly diluted, and the concentration is only PPM level, which is difficult to solubilize. However, surfactants improve the contact angle of the drug, improve the hydrophilicity of the drug, and promote the dissolution of the drug. Of course, surfactants may also increase drug absorption and prevent static electricity generated in the process.

If researchers have determined the critical micelle concentration (CMC), molar solubilization ratio (MSR) and curcumin (Cur) of different ratios of dodecyltrimethylammonium bromide (DTAB) and Tween 80 in alkali The degradation rate (k) in the aqueous solution (pH 13) and the surfactant compound alkaline solution is used to investigate the solubilization and protection of curcumin [2]. The results show that when Tween 80 is used alone, the solubilization ability is strong but the stability is poor; when DTAB is used alone, the stability is good but the solubilization ability is poor; the stability of the two is enhanced after the combination of the two in different ratios, when the DTAB mole fraction is At 0.4, the stability is the best. Although the solubilization ability is not the best at this time, compared to using DTAB alone, the MSR increases by 1.7 times. The surfactant compound can increase the solubility while increasing the stability.

A mixture formed by mixing oil, water, surfactant and co-surfactant is a microemulsion, which is widely used for the improvement and optimization of poorly soluble drugs.

3. Solid dispersion

A solid dispersion is a technology that uses one or two water-soluble carriers to mix with poorly soluble drugs, which destroys the internal crystal structure of the poorly soluble drugs and improves their energy state to improve the dissolution of poorly soluble drugs. This technology is currently the most commonly used technology. One of the methods used to improve the dissolution of poorly soluble drugs.

The above three technologies are common methods to improve the solubility of poorly soluble drugs. In addition, technologies such as inclusion compounds, polymer micelles, bimolecular matrix encapsulation and self-emulsifying drug delivery systems can be used to improve the solubility of poorly soluble drugs. Solubility. With the discovery and application of new preparation technologies, the limitations of the development and application of insoluble drugs will be broken, and the research methods of innovative pharmaceutical preparations will escort people’s health.

[1] Study on the dissolution of micronized cefdinir granules of raw materials [J].

[2] The solubilization and protection of curcumin by the complex of surfactants [J].



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