Gliclazide

Recent advances in Sustained Release Drug delivery System (SRDDS) aim to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance. This present study showed that the Gliclazide is an oral hypoglycemic (anti-diabetic drug) and is classified as a sulfonylurea. Its classification has been ambiguous, as literature used it as both a first generation and second generation sulfonylurea. Gliclazide was shown to protect human pancreatic beta-cells from hypoglycemia-induced apoptosis. It was shown to have an anti-atherogenic effect (preventing accumulation of fat in arteries) in type II diabetes. Gliclazide is used in the tablet form for antidiabetic effect.

The main focus of the present study was to explore co-crystallization technique to engineer pharmaceutical co-crystals of poorly aqueous soluble drug- Gliclazide (GLZ) using different GRAS listed coformers; benzoic acid (BA) and itaconic acid (IA). The complexation energy of GLZ and coformers were predicted by Quantum Mechanics method. Co-crystals in 1:2 molar ratios were formulated using solvent evaporation technique using acetone, a class III solvent as a medium for drug and coformer interaction at molecular level. The characteristics of GLZ and resultant co-crystals were evaluated in terms of flowability, drug content uniformity, saturation solubility and in-vitro dissolution studies. Further Fourier transformation infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to identify hydrogen bonding interaction, melting point, crystallinity and surface morphological characteristics of prepared co-crystals respectively. The obtained GLZ co-crystals indicated presence of additional peaks as well as band shifts in the infrared spectrum. Additionally DSC thermograph and XRD confirmed change in crystal lattice. The results of in-vitro dissolution indicated a significant enhancement in the dissolution profiles of both the co-crystals as compared to GLZ. Thus it could be concluded that the co-crystallization technique could be successfully exploited to develop new formulation of GLZ.

The aim of this study was to Design and Process Validate Bi-layer Tablet of Metformin Hydrochloride (MTH) and Gliclazide (GZ) effective for the treatment of Non-Insulin Dependent Diabetes Mellitus (NIDDM). For formulation of bi-layer tablet, initially both layer optimized individually. MTH and Gliclazide were formulated as sustained release layers (L1 and L2) by using various Hydrophilic polymers such as Methocel CR, HPMC K100, HPMC 15Cps and Methocel K100 LV. The effect of concentration of hydrophilic matrix (Methocel CR, HPMC 15Cps), binder (Polyvinyl Pyrollidone [PVP K90/PVP K30] on MTH and GZ drug release rate from matrix system was studied. The dissolution study of sustained release layer showed that an increasing amount of Methocel CR and HPMC or PVP K30/90 results in reduced drug release. Optimized batch of both drug formulations were used for formulation of bi-layer tablet. The rational for formulation of bi-layer tablet of these two drugs in combination was from class second generation sulphonylureas and biguanides was suitable for the treatment of NIDDM. Bi-layer tablet was suitable for preventing direct contact of these two drugs and maximize the efficacy of combination of two drugs for treatment of NIDDM.

In the present study compared and evaluated the three granulation process for controlled release antidiabetic drug of Gliclazide. The effect of three different polymers on the in-vitro dissolution profiles of Gliclazide controlled release tablet was studied. Later combinations of polymers were used and the tablets were prepared by using wet, dry and MADG (Moisture Activated Dry Granulation) process. The study was carried out using full factorial designs of experiments. The release rate of 5 to 6 mg%/ hour was targeted and the effect of the polymers on drug release over 24 hours was evaluated. The DOE experiments have shown that when the combination of polymer is used, the total polymer concentration should be in a narrow range of 32.4% w/w to 37.5% w/w in order to achieve the target dissolution profile for Gliclazide. The effect of three granulation process on the tablet properties and drug release were studied. Wet granulation and MADG process were compared. Finally MADG process is showing better results when compared with other process.

A simple, selective and rapid reverse phase high performance liquid chromatographic (RP-HPLC) method for the analysis of Gliclazide in bulk and in tablet dosage form has been developed and validated. Sample was analysed on a Enable C18 (250mm X 4.6 mm i.d, particle size 5μm) column. The mobile phase consist of Methanol: Water (pH 3.5) in the ratio of 85:15v/v which was sonicated to degased and delivered at a flow rate of 1ml/min at ambient temperature. The retention time of Gliclazidewas 3.7+0.02 minutes. Studies were performed using an HPLC system equipped with a UV detector; the response was monitored at 230 nm.The calibration curve was linear over the concentration range of 20-70 μg/ml (r2=0.999). The limit of detection for Gliclazide was found to be 0.2438 μg/ml and the limit of quantification limit was about 0.7388 μg/ml. The accuracy of the method was established based on the recovery studies. The proposed method can be applied to the routine analysis of Gliclazide in bulk and in tablet dosage form.

The main aim of present study is to formulation & optimize Gliclazide alginate microspheres by plackett burman’s factorial design. Which offers a flexible and easily controllable process for the manipulating the characteristics of the beads which is important in controlling the release rate and consequently the absorption of Gliclazide from the GIT, variation in polymer, concentration, time of gelation in the external phase were examined systemically for their effects on rate release and entrapment efficiency by Plackett Burman’s factorial design. The swelling behavior strongly depends on the polymer concentration. The result of the study will depends on the release profile of the drug from the formulation. The formulations follows zero order kinetics for the drug release. The in vitro release study indicates that the swelling is the main parameter in controlling the release rate from microcapsules.

  The objective of designing a dosage form is to achieve predictable therapeutic response to a drug included in a formulation which is capable of large scale manufacture with reproducible product quality. In order to ensure quality of product various features are required, like chemical and physical stability, preservation against microbial contamination, uniformity of dose of drug, acceptability to users including prescriber and patient, as well as suitable packing, labeling, and validation. The present research work focused on prospective process validation for the gliclazide 40mg tablet. Tablet was manufactured by wet granulation method. Formulation of tablet using Maize Starch, Avicel Ph 102, PVP-K30, sodium starch glycolate, Purified Talc, Aerosil 200 and  Magnesium stearate. Uniformity of dry mixing is excellent in 10min because % RSD found to be 0.4267-0.9021%. Granulating agent was prepared of desired consistency. Drying time 30 min is sufficient to achieve LOD 2-3%. Evaluation parameter of sizing shows effective LOD, % fine, BD & CI. Lubrication stage uniformity was achieved with 10min because % RSD found 0.8320-1.032% and flow properties was satisfactory. Compression machines optimum speed (20RPM) was satisfactory for effective compression. Based on results at each of the stages for the specified parameters it is concluded that gliclazide tablets can be effectively prepared with the desired specification & reproducible quality standards.