Meeting Manufacturing Challenges Tied to Extended-Release Injectables

Industry experts working with extended-release injectables discuss challenges and solutions to formulating and manufacturing these complex products.
May 02, 2012


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The industry has seen growth in extended-release (ER) injectables in recent years. These complex, long-term delivery products aim to reduce the number of injections a patient needs, for example, moving from once-a-day to once-a-month or less frequently. ER injectables can also ease patient compliance and relapse. They are most often used to treat pain management, drug and alcohol addictions, psychological and behavioral conditions (e.g., schizophrenia and depression), fertility, diabetes, and certain cancers.

One dominant type of an ER injectable product is polymer-based. This type includes microspheres, implants, and gels. These systems rely on diffusion through a polymer as well as erosion of that polymer to control release of the API. Another type involves conjugating a releasable chemical moiety to the active drug, thereby making a prodrug that is less soluble for slow uptake, or is slower to clear from the body. And another type would be insoluble salts.

According to Heidi Mansour, PhD, an assistant professor in the College of Pharmacy at the University of Kentucky and editorial advisory board member of Pharmaceutical Technology, these types of products are become more popular to manufacture because "scientific advances in polymer science and biomaterials have given rise to biocompatible and biodegradable polymers (e.g., various diblock and triblock copolymers) that offer a wide range in their temporal degradation profiles. As a result, there is a wide range in the temporal profiles of drug release for a wider range of drugs." In addition, she notes that, "there have been scientific and technological advances in particle engineering design methods, and in nanotechnology and tangible application to nanopharmaceuticals and nanomedicines."

Extended-release injectables are considered to be complex dosage forms by the regulatory authorities. These products bring key challenges to the manufacturing process, including: sterility assurance, the number of unit operations required, as well as comparability and control strategy concerns. Pharmaceutical Technology spoke to experts engaged in the development and manufacture of ER injectables to dig deeper into these challenges and to offer potential solutions.

Participating in the article are: Paul Herbert, vice-president of process development at Alkermes; Andrew J. Thiel, PhD, an associate research fellow, and David M. Loffredo, PhD, a director, both in Pharmaceutical Research and Development at Hospira; Mary Stickelmeyer, a research fellow with Eli Lilly and Company; and Arthur J. Tipton, PhD, head of Birmingham Laboratories within Evonik's Healthcare Pharma Polymers product line.