24/7 BIOPHARMA - issue 1 / October 2024

LLS HEALTH

number of pills needed per day. A gradual release mechanism, resulting in fewer sharp spikes in drug concentration, also has the potential advantage of minimizing adverse side effects. Combined, these benefits make extended-release medicines of great interest for both drug companies seeking their next commercial success and patients who wish to simplify their drug regimen. When embarking on an ambitious extended-release oral reformulation project, however, selecting the right excipients is crucial. Excipients, otherwise known as inactive ingredients, are key to creating robust formulations with better control over drug release profile. One efficient way to design an extended-release oral solid dosage form is by using a hydrophilic matrix former polymer. Using this approach, the active pharmaceutical ingredient (API), a matrix former polymer, and other excipients are mixed and compressed into tablets. Carbomers are effective matrix-forming excipients that can facilitate extended-release formulations. These comprise high molecular weight, crosslinked, acrylic acid-based polymers that are insoluble, and work by swelling in water to generate a hydrophilic gel matrix. Importantly, these excipients have demonstrated slower drug release rates at lower concentrations than other commercially available excipients. Typical usage levels in extended release tablets are only 5–30%, [4] enabling overall formulation cost savings and smaller tablet sizes Carbomers can also provide considerable formulation flexibility as they are compatible with a variety of APIs, excipients, and mainstream processing techniques – including direct compression, dry granulation (either through roller compaction or slugging) and wet granulation, involving high/low shear and extrusion spheronization methods. Enhancing drug release profiles with carbomers In short, by acting as a simple means to modulate drug release, working with versatile processing techniques, and providing multi-functional capabilities such as efficient binding and mucoadhesion, carbomers can be an invaluable tool for formulators.

matrix tablets is hydroxypropyl methylcellulose (hypromellose), a semisynthetic polymer derived from cellulose. Hypromellose is a linear polymer, meaning it is not chemically crosslinked and is, therefore, water soluble. It is by far the most common cellulose used to form swellable matrices, with its Generally Recognized as Safe (GRAS) classification encouraging its use. Hypromellose slows drug release by forming a gel layer around the tablet. Drug release is dependent on the diffusion and erosion rate. [5] Hypromellose can effectively slow drug release. However, as linear polymers such as hypromellose form matrices by physical entanglement, one issue associated with their use is that polymer levels of greater than 20% are necessary to form a coherent matrix. This is in contrast to chemically crosslinked polymers, such as carbomers, and the quantity of hypromellose needed can make reducing tablet size more difficult. When developing optimized extended-release tablets, it is important that formulators have access to a wide and varied toolbox. With this in mind, strategies that involve combining excipients for maximum effect are another possible means of optimizing extended release. The potential benefits of formulating with complementary excipients are wide-ranging. Firstly, there is the possibility of requiring lower total controlled release agent due to a favorable interaction, which can help to reduce tablet size. Flexibility in delivering target release profiles, A combined approach: carbomers and hypromellose

Hypromellose for extended-release formulations

Another example of a popular excipient that can facilitate the extended release of APIs from oral

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TWENTYFOURSEVENBIOPHARMA Issue 1 / October 2024