Drug powders are the main body of most pharmaceutical formulations, and their efficacy depends not only on the type of drug, but also to a large extent on the properties of the powders composing the pharmaceutical formulations. Numerous studies have shown that physical parameters such as specific surface area, pore size distribution and true density of drug powders are related to the properties of powder particles such as particle size, hygroscopicity, solubility, dissolution and compaction, and play an important role in the purification, processing, mixing, production and packaging capabilities of pharmaceuticals. Especially for APIs and pharmaceutical excipients, parameters such as specific surface area are important indicators of their performance.
The specific surface area of API, as the active ingredient of a drug, affects its properties such as solubility, particle size and solubility. Under certain conditions, the larger the specific surface area of the same weight of API, the smaller the particle size, dissolution and dissolution rate is also accelerated. By controlling the specific surface area of the API, it can also achieve a good uniformity and fluidity, to ensure uniform distribution of drug content.
Pharmaceutical excipients, as excipients and additional agents used in the production of drugs and prescriptions, specific surface area is one of the important functional indicators, which is important for diluents, binders, disintegrants, flow aids, and especially lubricants. For example, for lubricants, the specific surface area significantly affects their lubrication effect, because the prerequisite for lubricants to play a lubricating effect is to be able to be uniformly dispersed on the surface of the particles; generally speaking, the smaller the particle size, the larger the specific surface area, and the easier it is to be uniformly distributed during the mixing process.
Thus, accurate, rapid and effective testing of physical parameters such as specific surface area and true density of pharmaceutical powders has always been an indispensable and critical part of pharmaceutical research. Therefore, the methods for the determination of specific surface area and solid density of pharmaceutical powders are clearly defined in the United States Pharmacopoeia USP<846> and USP<699>, the European Pharmacopoeia Ph. Eur. 2.9.26 and Ph. Eur. 2.2.42, as well as in the second additions of the physical and chemical analysis contents 0991 and 0992 to the four general rules of the Chinese Pharmacopoeia, 2020 edition.
01 Gas adsorption technique and its application
Gas adsorption technique is one of the important methods for material surface property characterization. Based on adsorption analysis, it can accurately analyze the specific surface area, pore volume and pore size distribution, true density and other parameters of APIs, pharmaceutical excipients and drug formulations. In turn, it can do some basic analysis on the performance of drug expiration date, dissolution rate and efficacy, and help the rapid and high quality development of pharmaceutical industry.
Specific surface area: mainly has an important influence on the validity, dissolution rate and efficacy of drugs. Generally speaking, with a large specific surface area, the dissolution and dissolution rate will be accelerated accordingly, thus ensuring the uniform distribution of drug content; however, too large a specific surface area will make the drug adsorb more water, which is not conducive to the preservation and stability of drug efficacy.
Pore volume and pore size distribution: it has a key influence on drug disintegration, release and bioavailability. Larger pore volume can load various drugs in the pore channel, and can play a slow-release effect on the drug to improve the durability of the drug effect; in addition, the pore size increases within a certain range, the release rate of the drug will be correspondingly accelerated.
True density: it has an important influence on the fluidity, uniformity, compressibility, dissociation, crystallinity, etc. of the powder drug. The size of the true density can be used as a judgment of the crystallization state of the material and the percentage of solid content in the binary mixture; in addition, it has a certain guiding effect on the optimization of process parameters such as roll speed and roll pressure.
02 Practical application cases in the characterization of specific surface area and pore size distribution
(1) Characterization of specific surface area of the API montmorillonite dispersion
Montmorillonite, which is obtained by purification and processing of bentonite, has unique advantages in pharmacology because of its special layered crystal structure which makes it have good adsorption ability, cation exchange ability and water absorption and swelling ability. Its mechanism of action is closely related to its large specific surface area. Due to its large specific surface area, it can thus have a strong adsorption effect on toxic substances; in addition, it binds electrostatically with digestive tract mucus proteins and plays a protective and repairing role on the digestive tract mucosa.
The following is a case study of the characterization of montmorillonite dispersion powder material using the CIQTEK EASY-V series specific surface and pore size analyzer. According to the Chinese Pharmacopoeia 2020 version IV, nitrogen is used as the adsorbent, the area of the sample to be tested is at least >1m2 , and we recommend no less than 0.1g, which is heated and degassed under vacuum at 105°C for 2 hours before testing. The surface area of different types of montmorillonite dispersions has a large difference, 76.57 m2/g, 47.67 m2/g and 29.32 m2/g, respectively. The researcher can use the results of the specific surface area test to make a judgment of the basic medicinal properties and then select the corresponding type of raw material according to the actual action needs of the drug.
EASY-V series specific surface and pore size analyzer adopts static volume method testing principle, with fully automatic operation, humanized operation interface, easy to learn. The product technology has passed the scientific and technological achievement appraisal of the Federation of Machinery Industry, and has been purchased and used by universities and research laboratories in Europe and the United States, receiving unanimous praise.