Dokument: Orodispersible Tablets Containing Taste-Masked Lipid Pellets with Metformin Hydrochloride for Use by Elderly Patients
| Titel: | Orodispersible Tablets Containing Taste-Masked Lipid Pellets with Metformin Hydrochloride for Use by Elderly Patients | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=34667 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20150706-083726-1 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | MSc. Freire Petrovick, Gustavo [Autor] | |||||||
| Dateien: |
| |||||||
| Beitragende: | Prof. Dr. Breitkreutz, Jörg [Gutachter] Prof. Dr. Dr. h.c. Kleinebudde, Peter [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | Metformin HCl tablets encountered in the market show relatively inconvenient dimensions, decreasing the patient compliance during the treatment of type 2 diabetes mellitus. Furthermore, the crushing and dispersion of such a tablets in food or beverages exposes the unpleasant bitter taste of the API, which increases even more the nonadherence to treatment, especially by elderly patients. Therefore, this work focused on the development, manufacturing, and characterization of ODTs containing taste-masked lipid based micropellets of metformin HCl.
To obtained pellets presenting taste-masked properties a recently extrusion/spheronization methodology using solid lipids excipients was employed: solid lipid cold extrusion followed by spheronization (SLCE). The manufacturing of small diameter extrudates based on different quantitative and qualitative solid lipid binders were investigated. Extrudates presenting different drug release kinetics, correlated with the amount of lipid binders, were obtained. As the taste-masking principle of the SLCE is to modify the drug release of the API, reducing its contact with the taste buds in the oral cavity after drug administration, all extrudate formulations, even those presenting sustained release profiles, were further spheronized. The material temperature during the spheronization of lipid based extrudates was reported the most critical factor in SLCE/spheronization method. Although this issue was recently investigated, there are no reports in the literature suggesting a solution for this problem, especially if the formulation is based on a high amount of lipid binders. During the spheronization step process, high material temperatures led to stickiness of material fast particles agglomeration. Longer process times could not be achieved, avoiding the obtainment of spherical pellets. Therefore, a new approach to control this parameter was suggested. The employment of an alternative heating source on the conventional spheronizer was investigated. An IR light was used as external source of heat. The control of the IR light power supply provided an improved control of the material temperature during the entire process. This new control allowed to maintain the material temperature constant in a pre-defined and adequate range, avoiding material stickiness and the formation of agglomerates, even for extrudates based on higher lipid proportions. Despite qualitative and quantitative differences in the investigated formulations, the material temperature of each lipid extrudate was maintained at similar ranges. Micropellets exhibiting comparable shape and narrow particle size distributions were obtained and ARs below 1.3 were successfully achieved for the all investigated formulations, with exception of the PMHGT50, which showed a slightly higher value. Furthermore, the lipid micropellets based on more than 70% (w/w) of a lipid mixture containing hard fat, glyceryl distearate, and trimyristin showed prominent taste-masked properties due to a slower drug release within the first 2 min of dissolution. The micropellet formulation showing most prominent taste-masked properties and immediate drug release profile was chosen to the development of the ODTs. For the investigation of the impact of compression force and amount of two mannitol based ready-to-use excipients (Ludiflash® and Parteck® ODT) on the properties of tablets produced with these lipid micropellets, a DoE was performed. An eccentric press machine dotted of 15 mm flat-faced punches was used. The tablets based on Parteck® ODT showed a strong lamination phenomenon during the ejection phase. Therefore, it was not feasible to characterize these tablets and produce a DoE model to investigate the Parteck® ODT influences. Under those circumstances, only the DoE for the formulations based on Ludiflash® was evaluated. The increase in the compaction force led to an increase in the tensile strength and disintegration time of the tablets. On the other hand, the increase in the amount of Ludiflash® generates tablets exhibiting faster disintegration times and lower tensile strengths. Considering the specifications for tablets and ODTs in the Ph. Eur. (2014) regarding friability and disintegration time, a formulation containing 50% (w/w) of Ludiflash® and a compaction force of 7.5 kN were required to obtain adequate ODTs. Taste-masked properties and immediate drug release profile showed by the lipid micropellets were not influenced by the compression process. Moreover, the taste-masked properties of the ODTs were further improved by the establishment of a lag-time in the drug release profile. The presence of mannitol in the ready-to-use excipient showed a change on electronic tongue sensor responses, which indicated an improvement in the taste-masked properties. SEM images depicted that the lipid micropellets are deformed and do not suffer crush or breakage during the compaction step. ODTs presenting disintegration times below 2 min and exhibiting low friability and 500 mg of metformin were successfully produced. To conclude, SLCE/spheronization using a new spheronization process showed to be a robust method to better control the material temperature during the process and the quality of the produced pellets. A further direct compression of the lipid micropellets using Ludiflash® as disintegration excipient showed to be a feasible methodology to produce adequate taste-masked ODTs containing high drug load of metformin HCl. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 06.07.2015 | |||||||
| Dateien geändert am: | 06.07.2015 | |||||||
| Promotionsantrag am: | 08.05.2015 | |||||||
| Datum der Promotion: | 08.06.2015 |
