Capsules have a very long history. As early as 1500 BC, the first capsule was born in Egypt; in 1730, pharmacists in Vienna began to make capsules from starch; in 1834, the capsule manufacturing technology was patented in Paris; in 1846, the two-section hard capsule manufacturing technology has Obtained a patent in France; in 1872, the first capsule manufacturing and filling machine was born in France; in 1874, the industrial manufacturing of hard capsules began in Detroit, USA, and various models were launched at the same time.
Capsules are usually divided into hard capsules and soft capsules. Hard capsules, also known as hollow capsules, are composed of two parts of the cap body; soft capsules are processed into products from film-forming materials and contents at the same time. According to the raw materials, hollow capsules generally include: empty hard gelatin capsules and plant hollow capsules. At present, the large-scale production of plant hollow capsules in China is mainly empty HPMC capsules, so the current domestic hollow capsules are mainly empty hard gelatin capsules and hypromellose (HPMC) hollow capsules. Compare.
First, the raw materials used are different. The main component of empty hard gelatin capsules is high-quality medicinal gelatin. Gelatin is derived from collagen in animal skin, tendons, and bones, and is a protein partially hydrolyzed from collagen in animal connective tissue or epidermal tissue. The main component of empty HPMC capsules is 2-hypromellose, usually cellulose obtained by hydrolysis of plants, which is etherified. Due to religious beliefs (Judaism, Islam, etc.), dietary habits (vegetarianism), the need to advocate green nature, and the prevention of animal-derived diseases (mad cow disease), the use of plant capsules in the world is increasing year by year.
Second, the chemical structure stability of the shell is different. There are lysine residues in gelatin, the adjacent lysine residues are oxidized and deaminated to generate acetaldehyde groups, and the aldol-amine condensation reaction generates pyridine rings and cross-linking. Therefore, gelatin is used as the capsule material, and the capsules are placed during the placement process. There is a delay in disintegration. HPMC is part of methyl and part of polyhydroxypropyl ether of cellulose, with stable chemical properties and no cross-linking, so there will be no delay in disintegration. In addition, some groups containing aldehydes, reducing sugar-based compounds, and vitamin C in the content will react with amino or carboxyl groups in gelatin, and affect the disintegration of the capsule and the stability of the drug, so this type of drug is not suitable for use. Fits empty hard gelatin capsules. Gelatin contains groups such as carboxyl and amino groups, so the capsule shell will have an electrostatic effect. During the drug filling process, the capsule shell is prone to adhesion and easy adsorption of the contents. The HPMC capsule shell has little or no electrostatic effect.
Third, the water content is different. Under the condition of 20～25℃ and RH 40%～60%, the water content of empty hard gelatin capsules is about 13%～15%, and under this condition, the water content of empty HPMC capsules is about 4%～ 6%. Empty hard gelatin capsules become brittle below 10% water content, while empty HPMC capsules do not become brittle even up to 1% water content. Excessive water content has a great influence on the stability of moisture-sensitive drugs. For highly hygroscopic contents, if empty hard gelatin capsules are used, moisture will migrate from the capsule shell to the contents, and the capsule shell will become hard and brittle when the moisture drops, resulting in delayed disintegration, but empty HPMC capsules do not have this phenomenon.
Fourth, the coating properties are different. The surface of empty HPMC capsules is rougher than that of empty hard gelatin capsules, the affinity with most enteric coating materials is significantly higher than that of gelatin, and the speed and uniformity of coating material attachment are significantly better than that of gelatin, especially for the body-cap joint coating The reliability is significantly improved. It is not suitable to use organic solvents such as ethanol, which are easy to deform gelatin, and HPMC is chemically inert, so it can be used for aqueous coating and organic solvent coating such as ethanol. The good coating performance of HPMC makes it have obvious advantages in the preparation of slow-release and controlled-release coated capsules and targeted formulations.
Fifth, the additives are different. The main component of empty hard gelatin capsules is protein, so it is easy to breed bacteria and microorganisms. Preservatives and bacteriostatic agents need to be added during the production process, so that there may be residues on the capsules, and ethylene oxide must be used before the finished product is packaged. Alkane sterilization to ensure the microbial control index of the capsule. On the other hand, empty HPMC capsules do not require any preservatives during production and do not require ethylene oxide sterilization.
Sixth, the storage conditions are different. Tests have shown that HPMC capsules are almost invariable and brittle under low humidity conditions, do not generate static electricity, and remain stable under high humidity conditions. There is no problem in storage in all climatic zones, and there is no problem in transportation. Gelatin capsules are prone to sticking under high humidity conditions, hardening or brittle under low humidity conditions, are highly dependent on the temperature, humidity, humidity, and packaging materials of the storage environment, and even have higher requirements for transportation, especially In summer, a refrigerated truck is required to ensure the quality of the capsules.
To sum up, empty HPMC capsules have obvious advantages over empty hard gelatin capsules in many aspects. Although it is impossible to replace the dominant position of empty hard gelatin capsules in a short period, its application in medicine and health food applications will have a rapid growth trend.