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- Tajarobi, Farhad, 1971, et al.
(författare)
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Simultaneous probing of swelling, erosion and dissolution by NMR-microimaging – Effect of solubility of additives on HPMC matrix tablets
- 2009
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 37:2, s. 89-97
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Tidskriftsartikel (refereegranskat)abstract
- Extensive studies of extended release tablets based on hydrophilic polymers have illuminated severalaspects linked to their functionality. However, in some respects key factors affecting the mechanismsof release are yet unexplored. In the present study, a novel NMR-microimaging method has been usedto study the influence of the solubility of additives in extended release hydroxypropyl methylcellulose(HPMC) matrix tablets. During the course of the tablet dissolution the movement of the swelling anderosion fronts were studied simultaneously to the release of both polymer and additives. Moreover,the focused beam reflectance measurement (FBRM) technology was for the first time assessed for bothrelease and dissolution rate studies of poorly soluble particles. The studied formulations comprised solelyHPMC, 40% HPMC and 60% mannitol (Cs = 240 mg/ml) and 40% HPMC and 60% dicalcium phosphate (DCP)(Cs = 0.05 mg/ml). The dissolution rate of the tablets was highest for the HPMC/mannitol formulation,followed by HPMC/DCP and plain HPMC tablet. A contrasting order was found regarding the degree andkinetics of swelling. The results were interpreted in light of how the mass transport in the gel layer isinfluenced by the solubility of additives. A mechanistic model, considering osmotic pressure gradient andthe effective diffusion of the dissolution medium in the gel is proposed.
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| 2. |
- Tajarobi, Farhad, 1971, et al.
(författare)
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The Impact of Dose and Solubility of Additives on the Release from HPMC Matrix Tablets-Identifying Critical Conditions
- 2009
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Ingår i: Pharmaceutical Research. - : Springer Science and Business Media LLC. - 1573-904X .- 0724-8741. ; 26:6, s. 1496-1503
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. The dissolution of HPMC matrix tablets containing different amounts of highly soluble(mannitol) or poorly soluble (dicalcium phosphate, DCP) was studied to deduce the parameters criticalto release robustness.Methods. The release of HPMC and additives was studied using a modified USP II method at two paddlestirring rates, 50 and 125 rpm, at HPMC content varying from 15% to 100%.Results. At HPMC contents between 30% and 35% a critical point was identified and found crucial to therelease from the HPMC/mannitol tablets. Below this point the matrix rapidly disintegrated in a non robustmanner. At higher HPMC contents the mannitol release became increasingly diffusion controlled withmaintained matrix integrity. The release robustness was lower for HPMC/DCP than HPMC/mannitoltablets at high HPMC contents, however, lacking critical points. The critical point was interpreted as thepercolation threshold for HPMC and differences explained in terms of water transport into the matrix.Conclusion. The release robustness was lower for formulations with additives of low solubility having anerosion controlled release than for additives with higher solubility and a diffusion controlled release.However, for additives creating a steep osmotic pressure gradient, an HPMC content above thepercolation threshold becomes vital for maintaining the release robustness.
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| 3. |
- Unga, Johan, 1976, et al.
(författare)
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Relating solubility data of parabens in liquid PEG 400 to the behaviour of PEG 4000-parabens solid dispersions
- 2009
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 73:2, s. 260-268
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Tidskriftsartikel (refereegranskat)abstract
- The solid state behaviour of polyethylene glycol 4000 (PEG 4000) and dispersions of a homologous series of parabens (methyl- (MP), ethyl- (EP), propyl- (PP) and butyl- (BP)) were examined and compared to the paraben solubility in liquid PEG 400. Dispersions were prepared by co-melting different amounts of paraben (5-80% (w/w)) and PEG 4000 and were studied using a combination of differential scanning calorimetry (DSC) and small and wide angle X-ray diffraction (SAXD/WAXD). Depending on the concentration of parabens in the dispersions, DSC showed melting peaks from folded and unfolded forms of PEG, a eutectic melting and melting of pure parabens. The fraction of folded PEG increased and the melting temperatures of both PEG forms decreased with increasing paraben content. In an apparent phase diagram of PP-PEG dispersions a eutectic mixture appeared above 5% PP. In addition, a melting peak corresponding to the paraben appeared for dispersion containing more than 60% PP. Similar phase diagrams were shown for the other parabens. The SAXD data and a 1D correlation function analysis revealed that MP and BP were incorporated into the amorphous domains of the lamellae of solid PEG to a higher degree than EP and PP. In addition, the lamellae thickness of PEG and the fraction of amorphous domains increased more for MP and BP compared to EP and PP. BP showed the highest solubility of the parabens followed by MP, EP and PP in both liquid and solid PEG. Furthermore, the thickness of the amorphous domains of the PEG in the different parabens-PEG dispersions could be correlated to the solubility in liquid PEG 400.
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