Nateglinide

The objective of the present work was to formulate and evaluate novel self-nano emulsifying drug delivery system (SNEDDS) of poorly soluble drug Nateglinide. Poor water solubility and slow dissolution rate are major issues for most upcoming and existing biologically active pharmaceutical compounds. Nateglinide is Biopharmaceutical Classification System Class-II drug that has low solubility and high permeability. Surfactants and oil was selected based on solubility studies were further screened for their efficiency in formulation. Acrosyl K-135 was used as oil phase and Kolliphor RH 40 and Transcutol P were used as surfactant and co-surfactant respectively for formulation. Formulation F13 was found to be optimized formulation on the basis of in vitro dissolution studies, particle size and zeta potential. The particle size of the optimized SNEDDS formulation was found to be 74.6 nm and Z-Average was found to be 43.1 nm, indicating all the particles were in the nanometer range and the zeta potential of the optimized SNEDDS formulation was found to be -18.4 mV. The optimized formulation was then subjected to stability studies and was found to be stable after 6 months. Thus, the study confirmed that the SNEDDS formulation can be used as a possible alternative to traditional oral formulations of Nateglinide to improve its solubility.

Nateglinide is an anti-diabetic drug that lowers the blood glucose levels by stimulating insulin secretion from pancreas. Because of low solubility and bioavailability, its usage is limited. In the present study solid dispersions of Nateglinide were prepared by solvent evaporation method and evaluated through various steps for biological correlation. Nateglinide solid dispersions were prepared using PEG 6000, Pluronic F 127 and Labrafil M 1944. A 3-factor, 3-level Central composite design employed to study the effect of each independent variable on dependent variables. X-ray diffraction was used to analyze the crystallinity and FTIR was used to analyze the drug and excipient compatibility. Scanning electron microscopy was performed to analyze the surface of solid dispersion samples. The correlation coefficient showed that the release profile followed Higuchi model (R2= 0.95836). From Korsmeyer peppas model, the release exponent, n was found to be 0.80635 (0.43 < n < 0.85) and followed anomalous behaviour and hence release mechanism was indicative of diffusion. From in vitro dissolution studies it was proved that a Nateglinide solid dispersion may achieve good formulation capability for pharmaceutical manufacturer by increasing solubility and dissolution rate. Key words: Nateglinide, Diabetes mellitus, solid dispersions, solubility, Central composite  

The authors proposed a simple, rapid and sensitive liquid chromatography / tandem mass spectrometry assay method for the determination of nateglinide in human plasma using carbamazepine as internal standard (IS). Analyte and the IS were extracted from the human plasma via liquid-liquid extraction using ethyl acetate. The chromatographic separation was achieved on a C18 column by using a mixture of 0.1% formic acid buffer –acetonitrile buffer (20:80, v/v) as the mobile phase at a flow rate of 0.8 mL/min. The calibration curve obtained was linear (r2 ³ 0.99) over the concentration range of 10.0–10005 ng/mL. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The proposed method was found to be applicable to pharmacokinetic studies.

In present study long-acting biodegradable Nateglinide loaded Poly (lactic-co-glycolic) acid nanoparticleformulation is reported for treatment of Type 2 Diabetes Mellitus (T2DM).Different formulations were prepared by varying drug: polymer ratio (1:1, 1:2, and 1:3) and polyvinyl alcohol as stabilizer in 0.5-1.5% concentration range by emulsificationsolventevaporation technique. Optimization was carried out by evaluating entrapment efficiency and particle size. Optimized formulation was characterized for in vitro drug release, surface charge property, SEM, chemical incompatibility and invivo evaluated for blood glucose lowering property in rat model. The obtained resultsindicatethat formulation composition containing drug:polymer ratio 1:3 and stabilizer concentration 1.5%  gives high encapsulation efficiency (82.15%) with mean particle diameter of 216 nm and drug release for 72h. Drug release data was best fitted to Higuchi model indicating drug release was mainly took place by diffusion mechanism. Oraladministrationof optimized nanoparticle formulation showed two fold better activity as compared to standardNateglinide formulation(P

Nateglinide, an oral hypoglycemic agent is having disadvantage of low systemic bioavailability, poor absorption in upper intestinal tract, and short biological half life (1.5hr) for increasing the resident time of this drug in stomach spray drying technique used for preparation of mucoadhesive microspheres consist of different polymers like Hydroxypropyl Methycellulose (HPMC), Hydroxypropyl cellulose (HPC), Polyvinylpyrrolidone (PVP), Sodium alginate and ethyl cellulose with Nateglinide. The surface morphology and particle shape were studied by scanning electron microscope (SEM). The microspheres were evaluated for their micro encapsulation efficiency. The micro encapsulation efficiency of microspheres evaluated. Mucoadhesive microspheres prepared were spherical in shape, size in the range of 2.6-5μm.In vitro drug release performed for all the formulation and in vivo study of optimum formulation (F3) and pure Nateglinide in normal healthy rabbits performed. The micro encapsulation efficiency was in the range of 76.75 % - 89.36 % and microspheres of formulations (F1, F2, F3, F4, F6, and F7) have shown good mucoadhesive property. F3 had shown significant hypoglycaemic effect upto period from 5 hrs to 19 hrs, whereas pure Nateglinide showed the reduction of 39.85% after a period of 3hrs and reached normal with in 6.5hrs.

The present study describes a simple, accurate, precise and cost effective UV-VIS Spectrophotometric method for the estimation of Nateglinide, an anti-diabetic drug, in bulk and pharmaceutical dosage form. The solvent used was 0.1 N HCl+ 0.5 SLS solution and the λ max or the absorption maxima of the drug was found to be 212 nm. A linear response was observed in the range of 10- 60μg/ml with a regression coefficient of 0.999. The method was then validated for different parameters such as Linearity, Accuracy, Precision, Specificity, Robustness, Ruggedness, Limit of Detection and Limit of Quantification (LOQ). This method can be used for the determination of Nateglinide in quality control of formulation without interference of the excipients. Nateglinide was subjected to stress degradation under different conditions recommended by ICH such as acid, alkali, photolytic, dry heat and oxidative. The samples so generated were used for degradation studies using the developed method.