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By Selma Sahin and Nihan Izat

Selma SahinNihan IzatType 2 diabetes, described more thoroughly in an AAPS Blog post yesterday, is where the pancreas makes insulin but the body’s cells don’t use it correctly. To treat type 2 diabetes, we use oral antidiabetic drugs such as biguanide derivatives, sulfonylureas, thiazolidinediones, and alpha-glucosidase inhibitors. The decision about which medications to use depends on many factors, including blood sugar level and other health problems. The doctor may even combine drugs from different classes. One of the most frequently used combined drugs is metformin hydrochloride (HCl) and glyburide, even though they are both listed in the WHO Model List of Essential Medicines (PDF) as the only oral antidiabetic agents. On the market, there are conventional tablets containing these two drugs either alone or in combination. We are interested in preparing an orally disintegrating tablet (ODT) containing these two drugs because such a dosage form is not available in the market.

ODTs are designed to be dissolved on the tongue so that we do not need to chew the tablet or drink water to swallow these tablets. Also, ODTs provide comfort for patients who have difficulty in swallowing (e.g., geriatric, pediatric). Excipient selection is a critical point for designing ODTs and plays an important role in their quality and performance. We need different excipients to mask the taste, to disintegrate the tablet very rapidly (so called superdisintegrants), and to compress the tablet easily.

Glyburide dose is very low compared to metformin (2:500 mg), so that mixing them homogenously was the most crucial step in our formulation development. To overcome this problem, we prepared a metformin HCl and glyburide solution and spray dried them (Buchi B-290 mini spray dryer). We selected Ludiflash (for taste masking and as a disintegrant), Ac-Di-Sol (as superdisintegrant with a swelling degree as high as 230% in 30 minutes), magnesium stearate, and talc as the lubricants, and prepared the ODTs by the direct compression method. We performed various quality control tests on drugs-excipients powder mixture (e.g., angle of repose, compressibility index, bulk density and volume, apparent density and volume, swelling of superdisintegrant, powder moisture) and the ODTs (e.g., disintegration time, weight variation, content uniformity, diameter and thickness, friability, hardness, water absorption and dissolution). Our ODTs swelled at least twice the original size (Fig. 1), and disintegrated very rapidly (˂80 seconds).

The results of our quality control studies are very promising. Our formulation can be used as a base for further formulation development studies using different excipients with different amounts. ODTs for these two drugs will provide both patient compliance and rapid onset of action.

This work is being presented at the 2015 AAPS Annual Meeting and Exposition this week in Orlando.

fig1

Fig. 1 Swelling of metformin hydrochloride and glyburide containing ODT.

The authors would like to thank Tugba Gulsun, Yagmur Akdag Cayli, Mustafa Sinan Kaynak, and Levent Oner for their contributions to this abstract.

Selma Sahin is a professor of pharmaceutics at Hacettepe University Faculty of Pharmacy. Her research interests include pharmacokinetics, modelling and simulations, experimental diabetes and cirrhosis, intestinal and liver perfusion studies, drug transporters, and bioavailability and bioequivalence.
Nihan Izat is a Ph.D. student in the biopharmaceutics and pharmacokinetics program and works as a teaching and research assistant at Hacettepe University Faculty of Pharmacy. She is currently interested in formulation development, dissolution studies, and drug transporters.