RESUMEN
Lamotrigine is a BCS class II drug with pH dependent solubility. The bilayered gastric mucoadhesive tablets of lamotrigine were designed such that the drug and controlled release polymers were incorporated in the upper layer and the lower layer had the mucoadhesive polymers. The major ingredients selected for the upper layer were the drug and control release polymer (either HPMC K15M or polyox) while the lower MA layer predominantly comprised of Carbopol 974P. A 2(3) full factorial design was constructed for this study and the tablets were optimized for parameters like tablet size, shape, ex vivo mucoadhesive properties and unidirectional drug release. Oval tablets with an average size of 14 mm diameter were set optimum. Maximum mucoadhesive bond strength of 79.3 ± 0.91 * 10(3) dyn/cm(2) was achieved with carbopol when used in combination with a synergistic resin polymer. All the tested formulations presented a mucoadhesion time of greater than 12 h. The incorporation of methacrylic polymers in the lower layer ensured unidirectional drug release from the bilayered tablets. The unidirectional drug release was confirmed after comparing the dissolution results of paddle method with those of a modified basket method. Model independent similarity and dissimilarity factor methods were used for the comparison of dissolution results. Controlled drug release profiles with zero order kinetics were obtained with polyox and HPMC K15M which reported t 90% at 6th and 12th hours, respectively. The "n" value with polyox was 0.992 and that with HPMC K15M was 0.946 indicating an approximate case II transport. These two formulations showed the potential for oral administration of lamotrigine as bilayered gastric mucoadhesive tablets by yielding highest similarity factor values, 96.06 and 92.47, respectively, between the paddle and modified basket method dissolution release profiles apart from reporting the best tablet physical properties and maximum mucoadhesive strength.
RESUMEN
We hypothesise that the human infant, whether born prematurely or at term, may have special capacities when mounting a healing response to severe post-natal gastrointestinal injury consequent upon stem cells of endodermal origin, located in the infant gut, persisting beyond the intrauterine period. Should such endodermal stem cells persist beyond birth, and should they survive any gastro-intestinal injury, there would be a possibility for them to be re-activated, and then to differentiate into progeny cells appropriate to replacement of the destroyed intestinal cell type(s). We therefore postulate that in infants who survive significant intestinal necrosis requiring surgical excision in the perinatal period, a component of the recovery process may include some degree of intestinal regeneration. Evidence for the regeneration of intestine would be evinced by measurement of a biomarker in the plasma of recovering infants--alpha-fetoprotein (AFP)--as this protein would be produced by early generations of these putative replacement progeny intestinal cells. We would anticipate an initial significant rise in the plasma AFP, prior to a plateau in levels, and then a subsequent fall in plasma AFP values. This would indicate the activity, then subsequent cessation, of any intestinal cell regenerative process. We have recently published a previously undescribed pattern of anomalous serial plasma concentrations of AFP in several infants who survived following significant intestinal necrosis and subsequent surgical resection. We consider this novel hypothesis, and our associated observation of another cause of rising AFP in the post-natal period, to support our contention regarding the presence and potential of intestinal stem cells, and a regenerative process within the infant gastro-intestinal system. This hypothesis has important implications for the understanding of the physiologic responses following gut cell necrosis in the human newborn as well as future approaches to research directions, clinical support and potential treatment modalities, during their recovery phase. Further studies are needed to confirm our hypothesis.
