An in vitro study of the design and development of a novel doughnut-shaped minitablet for introaocular implantation

Y. E. Choonara, V. Pillay, T. Carmichael, M. P. Danckwerts
University of the Witwatersrand, Department of Pharmacy and Pharmacology & Department of Ophthalmology, South Africa

Medical Requirement

Disease due to cytomegalovirus (CMV) is among the most common opportunistic infections in patients with the acquired immune deficiency syndrome (AIDS).  The virus can give rise to multiple organ disease and may cause infections, retinitis (a serious sight-threatening infection) being one such example which accounts for 75-85% of CMV infections in patients.  If left untreated the disease inevitably results in blindness.

Intravitreal therapy is the preferable route of dosage adminstration due to its provision of higher intraocular drug concentrations but still remains a highly invasive method.  Among the most promising developments are intraocular implants/devices designed to deliver drugs with precision directly to the required areas offering several advantages to alternative therapies.  However such devices are extremely complicated to manufacture, are prohibitively expensive and (as they are not biodegrable) at the point of removal may increase the risk of wound leaking.

The objective was therefore to develop a small implantable doughnut-shaped minitablet and explore the physicochemical characteristics of this novel drug delivery system using poly(lactic-co-glycolic) acid polymer combinations in order to solve the problem of the implant not being biodegradable.  This bioerodible system would then not require removal once it has release its entire drug load and would be inexpensive and easy to manufacture as it is based on a tableting press fabrication.

Research Methods

The micromeritic properties, flowability and compressibility of the materials were investigated and evaluated for their suitability in fabricating the device.  Textural analysis was emplyed to characterise the compressibility of the polymers used in fabricating the device.  A TA.XTPlus Texture Analyser was fitted with a 3.125mm diameter ball probe and used to perform a indentation test.  The indentation hardness was represented by a conversion to the Brinell Hardness Number where:

BHN = 2F/(pi D(D2 - d2)^1/2)

where F is the force generated from indentation, D the diameter of the ball probe and d the indentation depth (0.25mm).

TA.XTPlus provides valuable results

PLGA can be regarded as suitably compressible for designing implantable devices such as the doughnut-shaped mini tablet using relatively compression forces which aid in trouble-free manufacturing with regard to wear on major tableting equipment such as punches and dies. The compact structure of the device was retained even after 24 weeks indicating that it is suitable as a biodegradable drug delivery system.  By careful selection of the type and concentration of polymer employed in formulating the device it was possible to produce a device that could release drug for any period up to 12 months which may be suitable for the treatment of CMV-R.