Résumé
The prolonged residence of drug formulation in the nasal cavity is of utmost importance for intranasal delivery of drug. Present investigation was aimed to develop a mucoadhesive in situ gel of Granisetron hydrochloride (GH) with reduced nasal mucocilliary clearance in order to improve the bioavailability of the antiemetic drug, granisetron hydrochloride. The in situ gelation upon contact with nasal mucosa was conferred via the use of the thermogelling Pluronic flake 127 (PF 127). Moringa gum (MG), carboxymethyl tamarind gum (CMTG) and sodium alginate (SA) was used to modulate mucoadhesion whereas drug release of optimized formulation was modified by 0.3% polyethylene glycol 6000 (PEG 6000). Results revealed that as the concentration of mucoadhesive polymer increased the mucoadhesive strength increased and gelation temperature decreased significantly. Preformulation studies showed that addition of GH in 18% PF 127 gels modulated gelation temperature significantly while mucoadhesive polymers alters mucoadhesion. Formulation F6, F11 and F15 showed more than 80% of drug diffusion at 240 min. Gelation temperature and mucoadhesive strength of all three formulations were found in the range of 30-31 C and 963.66±9.60 to 991.33±10.26 dyne/cm2 respectively. Formulation F11 showed optimum results and further histopathological evaluation reveled formulation is safe for use. Addition of PEG 6000 increased drug diffusion in formulation F11 with flux 0.034 mg.cm2/min. This study concluded the potential use of CMTG as mucoadhesive in situ nasal gel in terms of ease of administration, accuracy of dosing, prolonged nasal residence and improved nasal bioavailability.
Résumé
AIMS: To compare the performance of monoethylglycinexylidide (MEGX) test and conventional liver function tests (LFT) in differentiating between healthy volunteers and patients with different severity of liver cirrhosis, as judged using Child-Pugh (CP) classification. METHODS: One hundred and four patients with cirrhosis (CP class A, 47; B, 32; C, 25) and 25 healthy volunteers were studied between January 2005 to June 2006. In these subjects, conventional LFT were done, and serum specimens collected 15, 30 and 60 minutes after lidocaine injection were analyzed for MEGX. RESULTS: Conventional liver function tests showed minor differences between healthy volunteers and patients with Child class A, whereas these discriminated well between patients with Child class C and healthy volunteers. The changes in ALT, AST, bilirubin, albumin, AP and PT values were statistically significant in CP class B and C but not in class A when compared with healthy volunteers. MEGX concentration at 60 min was significantly higher in healthy volunteers (131.2 ng/mL) as compared to patients with cirrhosis (CP A - 51.3 ng/mL; CP B - 37.1 ng/mL; CP C - 17.3 ng/mL). There were significant differences (p <0.001) among all four groups (healthy volunteers and patients with CP classes A, B and C) for MEGX concentrations at each time point. MEGX test correlated well with CP scores (p <0.0001). CONCLUSION: MEGX test is a useful marker to stratify patients with liver cirrhosis based on liver function.