ABSTRACT
Inadequate skin permeability is the main challenge encountered in the transdermal drug delivery and to solve this crisis physical and chemical enhancement techniques are being developed. The aim of the present investigation was to study the combined effect of two such techniques, iontophoresis and esterification, on the transdermal delivery of atenolol. A series of ester prodrugs of atenolol were synthesized, characterized and studied for physicochemical properties and stability. In vitro permeation studies were carried out for atenolol and prodrugs at different donor concentrations (5, 10, and 20 mM) by passive process and iontophoresis (0.5 mA/cm(2)). Evaluation of the physicochemical parameters showed significant increase in lipophilicity and slight reduction in pK value in the ester prodrugs compared to parent drug. Stability studies revealed higher stability at pH 4 than pH 6. Prodrugs significantly enhanced the transdermal flux of atenolol in passive process while in iontophoresis the enhancement ranged from 1.4 to 2.7 fold compared to atenolol. In the prodrug series, permeation rate increased with increase in the length of alkyl side chain up to the addition of 5 carbon units, but thereafter no specific pattern was recorded in both passive and iontophoretic process. The steady state flux was highest in atenolol valerate (1.48 micromol/cm(2) h), which shows the promise of meeting the desired permeation rate (3.0- 31.0 micromol/ h) for maintenance of the therapeutic level in a 70 kg human.
Subject(s)
Atenolol/administration & dosage , Atenolol/metabolism , Iontophoresis/methods , Prodrugs/administration & dosage , Prodrugs/metabolism , Administration, Cutaneous , Animals , Atenolol/analogs & derivatives , Drug Stability , Esters/chemical synthesis , Esters/chemistry , Esters/metabolism , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Permeability , Prodrugs/chemical synthesis , Skin/metabolism , Skin Absorption/physiology , Solubility , Sus scrofaABSTRACT
OBJECTIVES: The objective of present study was to evaluate the effect of active principle (Cg-1) from Cassia glauca leaf on serum glucose and lipid profile in normal and diabetic rats. MATERIALS AND METHODS: Diabetes was induced by streptozotocin in neonates. Oral administration of petroleum ether, chloroform, acetone, and methanol of C. glauca leaf (100 mg/kg, p.o.) for 21 days caused a decrease in fasting blood glucose (FBG) in diabetic rats. Among all the extracts, acetone extract was found to lower the FBG level significantly in diabetic rats. Glibenclamide was used as standard antidiabetic drug (5 mg/kg, p.o). Acetone extract was subjected to column chromatography that led to isolation of an active principle, which was given trivial name Cg-1. Cg-1 (50 mg/kg, p.o.) was studied for its hypoglycemic and hypolipidemic potential. The unpaired t-test and analysis of variance (ANOVA) followed by post hoc test was used for statistical analysis. RESULTS: Cg-1 caused a significant reduction in FBG level. It also caused reduction in cholesterol, triglycerides, and LDL levels and improvement in the atherogenic index and HDL level in diabetic rats. CONCLUSION: Improvement in the FBG and the atherogenic index by Cg-1 indicates that Cg-1 has cardioprotective potential along with antidiabetic activity and provides a scientific rationale for the use as an antidiabetic agent.
ABSTRACT
Mucilage extracted from Ocimum gratissimum seeds, inertness and safety parameters established by a previous study was subjected to preformulation trial to assess its suitability as a pharmaceutical binder. Properties of the granules prepared with calcium carbonate using different concentrations of ocimum and compared with acacia (5%, w/w), as standard. Ocimum at 2.3% (w/w) level was found to be comparable with 5% (w/w) of acacia. Effect on drug release studied with paracetamol indicated that ocimum mucilage could be an alternative to acacia.
