A Novel Excipient for Orodispersible Minitablets
INTRODUCTION
The benefit of orodispersible minitablets (ODMT) for treating pediatrics has been demonstrated. The aim of this study is to determine the feasibility of a direct compression grade isomalt galenIQ™ 721,(BENEO-Palatinit) for producing ODMTs with hydrochlorothiazide (HCT) and enalapril-maleate (EM) as model drugs. The therapeutic need of these drugs for children is well known. Isomalt Ph. Eur. USP-NF, JP) is a disaccharide alcohol and belongs to the group of polyols. galenIQ™ 721 represents an agglomerated type isomalt manufactured by a fluid bed process followed by a sieving operation.
MATERIALS AND METHODS
Six formulations of ODMTs based on galenIQ™ 721 were directly compressed with 2 mm 19 tips punches on a rotary die press Pressima IMA Kilian) at a speed of 10 rpm containing either 30 8 of HCT (UNICHEM LABORATORIES) or 16 of EM (Kraemer Martin Pharma)Pharma)(Figure 1 The influence of 4 of the disintegrants Kollidon CL and CL SF ( on the disintegration time was evaluated The ODMTs were analyzed regarding disintegration time by a modified method 3 a n ODMT was put into a hull of Plexiglas with a height of 21 mm and 10 mm inside diameter The top and bottom of the hull were locked with mesh sieves of 710 µm The locked hull was put into a conventional disintegration apparatus according European Pharmacopoeia (Ph Eur and weighted with a hull made of metal Figure 2 Content uniformity was analyzed using HPLC according to European Pharmacopoeia 9 (Ph Eur 2 9 6 and dissolution profile according to USP methods in 37 55±0 55°C phosphate buffer pH 6 8 for EM and 0 1 N HCL for HCT using a basket apparatus The drug release was measured by UV Vis spectrophotometry (Lambda 40 PerkinElmer) Tensile strength was analyzed using a Texture Analyser (Stable Micro Systems) with a flat punch of 5 mm in diameter and a pre speed of 0 1 mm/s.
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RESULTS AND DISCUSSION
ODMTs based on galenIQ™ 721 were produced successfully Mechanical properties of the ODMTs were acceptable and the content uniformity requirements according Ph. Eu. 2. 9. 4. were achieved for all formulations. It was feasible to produce ODMTs without disintegrants to fulfill the requirements of Ph Eur regarding disintegration time. Even better results were obtained when using disintegrants (Table 1). The use of the modified method proved to be a promising tool for analyzing the disintegration of minitablets. A further advantage is the adaptability to the disintegration apparatus of the Ph. Eur. Dissolution studies showed full drug release of EM-ODMTs within 20 minutes. HCT ODMTs show 60 drug release within one hour fulfilling USP criteria for HCT (Figure 3 and 4). The differences in the dissolution profiles can be explained by the dissolution rate of the drug in the media and influence of the excipients. In further studies ODMTs based on galenIQ™ 721 with HCT and EM will be compared to existing formulations for ODMT. Furthermore, content uniformity according to Ph. Eur. 2. 9. 40. should be obtained. Stability data will be collected and analyzed regarding disintegration, tensile strength and dissolution.
See also the video on orodispersible minitablets
CONCLUSION
For the first time ODMTs based on galenIQ™ 721 were developed successfully by direct compression. Acceptable disintegration times and dissolution profiles as well as good mechanical properties of the minitablets indicate the suitability of galenIQ™ 721 for the production of ODMTs. Furthermore, the palatability and non cariogenic properties of galenIQ™ 721 can have a benefit for pediatrics.
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