Rhodamine-123: a p-glycoprotein marker complex with sodium lauryl sulfate

Aim of this study was to investigate the role of sodium lauryl sulfate [SLS] as P- glycoprotein inhibitor. The everted rat gut sac model was used to study in-vitro mucosal to serosal transport of Rhodamine-123 [Rho-123]. Surprisingly, SLS decreases the serosal absorption of Rho-123 at all investigated concentrations. Investigation reveals complex formation between Rhodamine-123 and sodium lauryl sulfate. Interaction profile of SLS and Rho-123 was studied at variable SLS concentrations. The SLS concentration higher than critical micelle concentration [CMC] increases the solubility of Rho-123 but could not help in serosal absorption, on the contrary the absorption of Rho-123 decreased. Rho-123 and SLS form pink color complex at sub-CMC. The SLS concentrations below CMC decrease the solubility of Rho-123. For further studies, Rho-123 and SLS complex was prepared by using solvent evaporation technique and characterized by using differential scanning calorimeter [DSC]. Thermal analysis also proved the formation of complex between SLS and Rho-123. The P values were found to be significant [<0.05] except group comprising 0.0001% SLS, and that is because 0.0001% SLS is seems to be very low to affect the solubility or complexation of Rho-123

Influence of intestinal efflux pumps on the absorption and transport of furosemide

Furosemide is a commonly used diuretic which is used in the treatment of edema, congestive heart failure, hypertension and renal failure. Its absorption exhibits inter-and intra- subject variability that can be attributed to many factors including the intestinal efflux pumps such as the P-glycoprotein [P-gp]. This study was done due to the great disagreement between what is published in the literature regarding the influence of P-gp on furosemide and at the same time due to the importance of this drug in the treatment of different conditions as described above. In addition, an investigation of the effect of two of the commonly used pharmaceutical excipients [hydroxypropyl beta-cyclodextrin [HP beta CD] and Tween 80] and also a P-gp inhibitor [verapamil hydrochloride] on the intestinal absorption of this drug were also done. The study utilized the everted intestinal sacs technique to investigate both the effect of the efflux transporter [P-gp] on furosemide absorption and also the effect of the chosen excipients. The absorption of furosemide was significantly influenced by the P-gp as confirmed by the everted vis the non-everted sacs together with the verapamil study in which the transport of furosemmide was inhibited by verapamil. In addition, Tween 80 was also shown to inhibit the P-gp pump whereas the HP beta CD did not significantly influence the efflux of furosemide in this study. P-glycoprotein and some of the used excipients in the formulation play a very important role in the transport of furosemide and other drugs. Thus excipients that affect the activity of P-gp should be avoided when formulating drugs that are substrate for the P-gp or other efflux pumps

Preparation and evaluation of a new gastro-retentive extended release meclozine hydrochloride tablets

The conventional sustained release formulations are not suitable for drugs exhibiting a narrow window of absorption. For example, Meclozine, is highly soluble in only the gastric fluid and usually prescribed for patients who are experiencing nausea and vomiting and thus the risk of loosing the administered dose is always present. For this reason, any drug delivery system that is capable of keeping the drug in the stomach for a longer time wilt be advantageous. One approach to achieve this is the gasiroretentive delivery systems. In this study, twelve formulae of Meclozine HCI tablets were prepared and evaluated for the uniformity of weight, hardness, friability, water uptake, and the percentage of increase in tablet weight. The in-vitro bioadhesion of the prepared formulae was evaluated using chicken pouches method. The in-vitro release studies of the prepared tablets were done and the percentage of drug released was calculated Finally, the appropriate release model that describes the pattern of drug release was determined The prepared tablets exhibited different disintegration and swelling profiles according to the type and amount of the bioadhesive polymer incorporated into the formula. All the prepared tablet formulae complied with the requirement of USP XXIV with regard to uniformity of weight and drug content. The mucoadhesive force of the investigated mucoadhesive polymers was found to be in the following order.' CMC> HPMC> HPC> CP. Formulae containing HPMC and HPC showed a promising in-vitro release and adhesion results