Microencapsulation technology is widely gaining acceptance in agrochemicals, consumer care items, textiles, and adhesives and has been used in copy paper and elsewhere for decades. The act of encapsulating tiny active particles, generally from 1 to 1000 microns in diameter, from ambient conditions serves to protect them until such time when their active properties are needed. It economizes pesticide use, extends the effectiveness of deodorant, makes clothing more resistant to bacteria, and enables multiple copies without carbon paper.
While microencapsulation is already a widely accepted method of drug delivery, the aforementioned and other companies must continue to innovate in order to accommodate more sophisticated molecules. As biological assays are further refined and physiological responses are better understood, new chemical entities (NCEs) are becoming increasingly potent. Many of the new pharmaceutical compounds are extremely insoluble, requiring solubilization technologies to enhance bio-availability.
Particle size is also a deciding factor when selecting the appropriate microencapsulation technology for a given delivery route. For example, most injectable particles are ideally 20 to 80 microns in diameter. Smaller particle sizes increase the surface area-to-volume ratio, making them more readily soluble when encapsulated in smaller particle sizes, and thus more easily assimilated by the human body.
Frost & Sullivan has identified 37 microencapsulated prescription drugs marketed in the United States, of which over half are delivered orally. Injectable therapeutics account for more than one-third of the total, with the remaining balance distributed among dermal and ocular applications.
Oral Delivery
Microencapsulated APIs in tablets often achieve the desired release profile in combination with a solid matrix or enteric coating that slows the exposure of API to the digestive tract. Tableting technologies are proven, generally stable, and inexpensive for manufacturers, as well as compact, portable, and easy to self-administer for consumers. Furthermore, the intestinal epithelium has a total surface area of approximately 200 sq meters, giving the API ample surface area through which to diffuse.
A fine example of an orally administered microencapsulated drug is Cipro XR. Bayer submitted a New Drug Application (NDA) in October 2002 to market Cipro XR (extended release) as a once-daily tablet to treat urinary tract infections (UTIs). The new 24-hour formulation uses a bi-layer matrix of active ingredients. In addition, Bayer jointly developed a once-daily form of Cipro-OD with Ranbaxy Laboratories of India. Because the drug was scheduled to lose patent protection in December 2003, Cipro XR's upgraded performance not only extends the product life, but also provides Bayer with additional exclusivity for the same molecule.
Biologics: Additional Opportunities For Injectables
Advances in injectable drug delivery have made for smarter molecules that can stay in the bloodstream longer with fewer side effects. Microencapsulation allows for less-frequent injections, longer-lasting half-lives of drugs, more sophisticated site targeting, and reduced toxicity.
The harsh conditions in the stomach denature most peptides and proteins, rendering some conventional oral delivery routes useless for biologics. Consequently, they must be injected, and in order to achieve reasonable patient compliance, they require some sort of depot or extended release, which can already be done with existing polymeric encapsulation techniques.
Dermal & Other Routes
Dwarfed by oral and injection delivery routes, nearly all dermal, ophthalmic, and inhalation therapeutics with microencapsulation technologies remain in clinical trials. Skin thickness and blood flow in the skin do vary with age, sex, and other characteristics. Yet for dermal applications, the skin is usually a difficult barrier for pharmaceutical molecules to penetrate, particularly those with high molecular weights. Even among those drugs in small enough particles to pass through the skin, permeation rates pose another potential obstacle to microencapsulated transdermal drug delivery. Another general detraction from dermal and ocular application is the poten-tial for rashes or other unsightly physical responses to treatment.
A number of companies are involved in pulmonary drug delivery, particularly for inhalable insulin. The concept of sustained release in the lungs is particularly tricky due to challenges associated with cilia and particle residence time considerations when excipients are chronically deposited in the lungs over extended periods. Furthermore, microencapsulation is not always required for particle atomization.
Overcoming Physiological Barriers
Beyond improved performance, microencapsulation offers strategic advantages in the delivery of therapeutic molecules. Performance advantages for an NCE may lead to the displacement of less-sophisticated incumbents in the market. For existing APIs, re-engineering with microencapsulation can generate new proprietary variations of a drug, creating a platform for another NDA, and additional patent protection with which to fend off generic competition.