In the centuries of capsules, gelatin has maintained it […]
In the centuries of capsules, gelatin has maintained its position as a mainstream capsule with its wide range of sources, stable physicochemical properties and excellent processing properties. With the increasing preference for capsules, hollow capsules are more widely used in the fields of food, medicine and health care products.
However, the occurrence and spread of mad cow disease and foot-and-mouth disease have caused people to start worrying about animal-derived products. The raw materials commonly used in gelatin are the bone and skin of cattle and pigs, and their risks are gradually attracting people's attention. In order to reduce the safety risk of hollow capsule raw materials, industry experts continue to research and develop suitable plant-derived capsules.
In addition, with the increase in the variety of capsules, the diversity of its contents has gradually made people realize that gelatin hollow capsules have compatibility problems with some contents with special properties. For example, content containing an aldehyde group or reacting under certain conditions to form an aldehyde group may lead to cross-linking of gelatin; a highly reductive content may react with gelatin in Maillard (Mailard) Reaction); the moisture-absorbing content will make the capsule shell lose water and lose its original toughness. The stability problem of the above gelatin hollow capsules has attracted more attention for the development of new capsule materials.
Which plant-derived materials are suitable for the production of hollow hard capsules? People have tried a lot. Chinese Patent Application No. 200810061238.X applies sodium sulphate as the main capsule material; 200510013285.3 applies starch or starch composition as the main capsule material; Wang GM  reports the manufacture of hollow capsules from chitosan capsule raw materials. Zhang Xiaoju et al  reported products with konjac-soy protein as the main capsule material. Of course, the most studied is the cellulose material. Among them, hollow capsules made of hydroxypropylmethylcellulose (HPMC) have been formed into a large-scale production.
HPMC is widely used in the field of food and medicine. It is a commonly used pharmaceutical excipient, which is included in the Pharmacopoeia of all countries. FDA and EU approve HPMC as a direct or indirect food additive; GRAS is contained as a safe substance, No. GRN 000213; JECFA database, INS No.464, did not limit the daily amount of HPMC dosage; in 1997, the Ministry of Health approved it as a food additive, thickener (No. 20), suitable for all kinds of food Add [2-9] according to the production requirements. Due to the difference in the nature of gelatin, the prescription of HPMC hollow capsules is more complicated, and it is necessary to add some gelling agents such as gum arabic, carrageenan (seaweed), starch and the like.
HPMC Hollow Capsule is a product with a natural concept. Its material and production process are recognized by the Jewish, Islamic and Vegetarian Associations. It can meet the needs of people of various religious and dietary habits and has a high degree of acceptance. In addition, HPMC hollow capsules have the following unique properties:
Low water content - about 60% lower than gelatin hollow capsules
The water content of gelatin hollow capsules is generally from 12.5% to 17.5% . The temperature and humidity of the environment should be controlled within a suitable range during the production, transportation, use and storage of hollow capsules. A suitable temperature is 15-25 ° C and a relative humidity of 35%-65% in order to maintain the performance of the product for a long time. The HPMC membrane contains very low moisture, typically 4% to 5%, which is about 60% lower than the water content of gelatin hollow capsules (Fig 1.). Exchange of moisture with the environment during long-term storage will increase the water content of the HPMC hollow capsules in the specified package, but will not exceed 9% within 5 years.
The low water content makes HPMC hollow capsules suitable for the filling of hygroscopic or moisture sensitive contents to extend the shelf life of the product.
In a 2005 study by DSM Nutrition, the effects of HPMC hollow capsules (Vcaps®) and gelatin hollow capsules on the stability of probiotics (Lafti® L-10 Lactobacillus acidophilus) were compared. Probiotics are a class of living microorganisms. Oral administration of a sufficient number of probiotics can improve the balance of the host gut microbes for the treatment of intestinal diseases. It is generally believed that only living bacteria can produce probiotic functions. However, probiotics are very sensitive to moisture, and excessive water can cause the death of live bacteria . DSM filled Lafti® L -10 and excipients into HPMC capsules and gelatin hollow capsules under different humidities and examined their stability. The results show that compared with gelatin hollow capsules, HPMC hollow capsules can better maintain the viable count of the product and prolong the efficacy of probiotic products (Fig 2.)
High toughness, no brittle
As mentioned above, the gelatin film has a specified moisture content, and if it is below this limit, the gelatin film will undergo significant friability. Ordinary gelatin hollow capsules without any additives have a risk of friability of more than 10% at a moisture content of 10%; 100% friability occurs when the moisture is continuously reduced to 5%. In contrast, HPMC hollow capsules have much better toughness and maintain good performance even at low ambient humidity (Fig 3). Of course, the incidence of friability of HPMC hollow capsules with different prescriptions at low humidity will vary greatly.
Conversely, gelatin hollow capsules are placed in a high-humidity environment, and the shells become soft, deformed, and even collapsed when they absorb water. HPMC hollow capsules maintain good morphology and performance even under high humidity conditions. Therefore, HPMC hollow capsules are highly adaptable to the environment. This advantage is particularly significant when the product's sales area covers multiple climatic zones or storage conditions are relatively poor.
Strong chemical stability
The cross-linking reaction of gelatin capsules is a thorny problem encountered with capsule formulations. Since the aldehyde group of the content reacts with the amino group of the amino acid in the gelatin to form a network structure, the capsule shell is difficult to dissolve under the dissolution condition in vitro, thereby affecting the release of the drug. Hypromellose is a cellulose derivative that is chemically inert and has excellent compatibility with most materials. Therefore, HPMC hollow capsules have no risk of cross-linking and have high chemical stability (Fig. 4).
Good coating performance
Enteric capsules are used for drugs that are susceptible to gastric acid damage, irritating to the gastric mucosa, or require targeted administration. The internationally accepted enteric capsule process is an integral coating of enteric pellets and capsules. HPMC hollow capsules show unique advantages in the overall capsule coating.
Studies have shown that due to the rough surface of HPMC hollow capsules (Fig 5), the affinity with most enteric coating materials is significantly higher than that of gelatin. The speed and uniformity of coating materials are significantly better than gelatin, especially the combination of body caps. The reliability of the coating is significantly improved. In vitro dissolution testing showed that the HPMC capsules had a lower permeability in the stomach and a good release in the intestine .
The properties of HPMC hollow capsules continue to broaden their application. From all-natural products to moisture-sensitive or hygroscopic content, there are now unique applications in dry powder inhalants and enteric coatings. It should be noted that the HPMC hollow capsules currently listed at home and abroad have relatively high oxygen permeability, and the disintegration is slightly slower than the gelatin hollow capsules, but the bioavailability in vivo is similar , which should be considered in the research and development.
As we all know, from laboratory research, large-scale experiments, industrial production to market-oriented promotion, we have to go a long way. This is why, after years of research and development, only a few hollow-capsule products of plant-derived materials have been successfully listed. In 1997, Capsugel was the first to market HPMC Hollow Capsules VcapsTM in the United States, providing a new option for oral capsules. At present, the annual sales volume of HPMC hollow capsules in the world has exceeded 20 billion, and it is growing at a rate of 25% per year.