Hard capsules/HPMC hollow capsules/vegetable capsules/high-efficiency API and moisture-sensitive ingredients/film science/sustained release control/OSD engineering technology….
Outstanding cost-effectiveness, relative ease of manufacture, and ease of patient control of dosage, oral solid dosage (OSD) products remain the preferred form of administration for drug developers.
Of the 38 new small molecule entities (NMEs) approved by the U.S. Food and Drug Administration in 2019, 26 were OSD1. In 2018, the market revenue of OSD-branded products with secondary processing by CMOs in the North American market was approximately $7.2 billion USD 2. The small molecule outsourcing market is expected to exceed USD 69 billion in 20243. All of these data suggest that oral solid dosage forms (OSDs) will continue to prevail.
Tablets still dominate the OSD market, but hard capsules are becoming an increasingly attractive alternative. This is partly due to the reliability of capsules as a mode of administration, especially those with high potency antitumor APIs. Capsules are more intimate to patients, mask unpleasant odors and tastes, and are easier to swallow, significantly better than other dosage forms.
Julien Lamps, Product Manager at Lonza Capsules and Health Ingredients, discusses the various advantages of hard capsules over tablets. He shares his insights into hydroxypropyl methylcellulose (HPMC) hollow capsules and how they can help drug developers optimize their products while meeting consumer demand for plant-derived medicines.
Hard capsules: Improve patient compliance and optimize performance
Patients often struggle with medicines that taste or smell bad, are difficult to swallow, or may have adverse effects. With this in mind, developing user-friendly dosage forms could improve patient compliance with treatment regimens. Hard capsules are an attractive option for patients because, in addition to masking taste and odor, they can be taken less frequently, reduce tablet burden, and have better release times, through the use of immediate-release, controlled-release and slow release to achieve.
Better control over the release behavior of a drug, for example by micropelletizing the API, can prevent dose dumping and reduce side effects. Drug developers are finding that combining multiparticulate technology with capsules increases the flexibility and effectiveness of controlled-release API processing. It can even support pellets containing different APIs in the same capsule, which means that multiple drugs can be administered simultaneously in different doses, further reducing the frequency of dosing.
The pharmacokinetic and pharmacodynamic behaviors of these formulations, including the multiparticulate system4, extrusion spheronization API3, and the fixed-dose combination system5, also showed better reproducibility compared to conventional formulations.
It is because of this potential improvement in patient compliance and efficacy that the market demand for granular APIs encapsulated in hard capsules continues to grow.
Polymer preference:
The need for vegetable capsules to replace hard gelatin capsules
Traditional hard capsules are made of gelatin, however, gelatin hard capsules can present challenges when encountering hygroscopic or moisture-sensitive contents. Gelatin is an animal-derived by-product that is prone to cross-linking reactions that affect dissolution behavior, and has a relatively high water content to maintain its flexibility, but may also exchange water with APIs and excipients.
In addition to the impact of capsule material on product performance, more and more patients are reluctant to ingest animal products for social or cultural reasons and are seeking plant-derived or vegan medicines. To meet this need, pharmaceutical companies are also continuing to invest in innovative dosing regimens to develop plant-based alternatives that are both safe and effective. Advances in materials science have made plant-derived hollow capsules possible, offering patients a non-animal-derived option in addition to the advantages of gelatin capsules—swallowability, ease of manufacture, and cost-effectiveness.
For better dissolution and compatibility:
Application of HPMC
Currently, one of the best alternatives to gelatin is hydroxypropyl methylcellulose (HPMC), a polymer derived from tree fibers.
HPMC is less chemically inert than gelatin and also absorbs less water than gelatin6. The low water content of HPMC capsules reduces water exchange between the capsule and the contents, which in some cases can improve the chemical and physical stability of the formulation, extend shelf life, and easily meet the challenges of hygroscopic APIs and excipients. HPMC hollow capsules are insensitive to temperature and easier to store and transport.
With the increase of high-efficiency APIs, the requirements for formulations are becoming more and more complex. So far, drug developers have achieved very positive results in the process of exploring the use of HPMC capsules to replace traditional gelatin capsules. In fact, HPMC capsules are currently generally preferred in clinical trials due to their good compatibility with most drugs and excipients7.
Continued improvements in HPMC capsule technology also mean that drug developers are better able to take advantage of its dissolution parameters and compatibility with a wide range of NMEs, including highly potent compounds.
HPMC capsules without gelling agent have excellent dissolution properties without ion and pH dependence, so that patients will get the same therapeutic effect when taking the drug on an empty stomach or with meals. As shown in Figure 1. 8
As a result, improvements in dissolution may allow patients to have no qualms about scheduling their doses, thereby increasing compliance.
In addition, continued innovation in HPMC capsule membrane solutions can also enable intestinal protection and rapid release in specific areas of the digestive tract, targeted drug delivery for some therapeutic approaches, and further enhance the potential applications of HPMC capsules.
Another application direction for HPMC capsules is in inhalation devices for pulmonary administration. Market demand continues to grow due to improved bioavailability by avoiding the hepatic first-pass effect and providing a more direct route of administration when targeting diseases such as asthma and chronic obstructive pulmonary disease (COPD) with this form of administration .
Drug manufacturers are always looking to develop cost-effective, patient-friendly, and effective treatments for respiratory diseases, and to explore inhaled drug delivery treatments for some central nervous system (CNS) diseases. demand is increasing.
The low water content of HPMC capsules makes them ideal for hygroscopic or water-sensitive APIs, although electrostatic properties between formulation and hollow capsules must also be considered throughout development8.
final thoughts
The development of membrane science and OSD engineering technology has laid the foundation for HPMC capsules to replace gelatin capsules in some formulations, providing more options in optimizing product performance. In addition, increasing emphasis on consumer preferences and rising demand for inexpensive inhaled drugs have boosted the demand for hollow capsules with better compatibility with moisture-sensitive molecules.
However, the choice of membrane material is key to ensuring the success of the product, and the right choice between gelatin and HPMC can only be made with the right expertise. The correct choice of membrane material can not only improve the efficacy and reduce adverse reactions, but also help overcome certain formulation challenges.