No abstract

The crucial endeavor in this method is focused on the study analysing recovery and column efficiency (theoretical plate) after extraction of metoclopramide from PVP K30-Metoclopramide (3:1 w/w) solid dispersion (SD). The proposed work also presents a reversed-phase high performance liquid chromatography method for the detection of very small amount of metoclopramide base followed by different analytical techniques. In this context, it may be noted that the values of limit of detection (LOD) and limit of quantitation (LOQ) for the metoclopramide base as obtained are, 0.052 µg/mL and 0.159 µg/mL respectively. The linearity is performed in the range of 2-20 µg/ mL; performance of column remained satisfactory throughout the analysis, N = 4927-2434. The percentage recovery of pure and extracted metoclopramide ranges from 103-105% and 86-120% approximately. The results collectively demonstrate that the proposed method is selective. Clear isolation of metoclopramide from SD is achieved without any solid state interference.

Chemotherapy induced nausea and vomiting (CINV) is an issue, which usually occurs in cancer patient. Despite high bioavailability of oral and intravenous administration, these have some drawbacks. The oral route causes hepatic first pass metabolism and intravenous route is invasive in nature. Hence, antiemetic drug by means of transdermal route is necessary to administer in such cases. The aim of the present investigation is to develop suitable Transdermal Therapeutic System (TTS) with an objective to enhance solubility and skin permeability properties of metoclopramide base. Preformulation study begins with an approach to enhance solubility of 40 metoclopramide base by solid dispersion technique. transdermal films were prepared with 41 the solid dispersion as well as with pure drug. Phase solubility study at various temperatures reveals binding constants (Ka, 95-350 M-1 for PVP K30; 56-81 M-1 for HPβCD). Spontaneity of solubilization was justified by AL type linear profiles. The films showed satisfactory diffusion (%), permeation rate and flux after 8 h study. The transdermal patches as prepared were analyzed under FTIR, DSC and SEM. Both solubility and permeability rate in this investigation have been enhanced. So, it can be affirmed that this route would effectively enhance bioavailability.

Chemotherapy induced nausea and vomiting (CINV) and post-operative nausea and vomiting (PONV) is a problem, often occurs in patient. Inspite of high bioavailability, the demerits such as: hepatic first pass metabolism and invasive nature of oral and parenteral dosage forms can be avoided with anti-emetic therapy of transdermal device. The major objective of the present study is to modify the hydrochloride (HCl) form of Ondansetron (OND) to the base form followed by improvement of solubility and permeability of OND by employing solid dispersion (SD) loaded patches. Preformulation study, as observed, begins with an approach to enthuse solubility of OND by SD technique choosing different carriers. The choice of carriers was rationalized by phase solubility study. Several combinations of transdermal films were prepared with pure drug, carriers and SDs with plasticizer Ka values of OND-HPβCD binary system were found lower (54.43 to 187.57 M -1 ) than that of OND-PVP K-30 binary system (1156.77 to 12203.6 M -1 ). The drug content of SDs and patches were found satisfactory. Better permeation rate (236.48±3.66 µg/3.935 cm 2 ) with promising flux enhancement (8.30 fold) was found with DBP loaded SD patch (P6*). Hence, enhancement of solubility and permeability of P6* ensures that it can successfully enhance the bioavailability.