Glipizide

In this study Β-Cyclodextrin facilitated Nanosponges were prepared by the solvent evaporation technique and subsequently formulated in a tablet form for immediate release of Glipizide. The Nanosponges formulations were prepared by solvent evaporation method employing Β-Cyclodextrin as a polymer. The compatibility of the drug with formulation components was established by Fourier Transform Infra-Red (FTIR) spectroscopy. The surface morphology, particle size, production yield, and drug entrapment efficiency of Nanosponges were examined. Shape and surface morphology of the Nanosponges were examined using scanningelectron microscopy. Particle size of prepared Nanosponges was observed in the range of 428.7  to  633.5nm. Scanning electron microscopy revealed the porous, spherical nature of the Nanosponges.SEM photographs revealed the spherical nature of the Nanosponges in all variations; however, at higher ratios, drug crystals were observed on the nanosponge surface. Increase in the drug/polymer ratio (1:1 to 1:3) increased their yield (10.23 ± to 35.69), which is in increasing order due to the increase in the concentration of polymer but after certain concentration it was observed that as the ratio of drug to polymer was increased, the particle size decreased, the drug content of different formulations was found in the range 94.4to 98.6%,the entrapment efficiency of different formulations were found in the range of 82.11 to 94.40%, the drug  release of the Optimized formulation was found to be 97.71%.

The present investigation was aimed to develop Glipizide loadedproliopsomal carrier system for Transdermal drug delivery which, deliver the drug effectively over an extended period of time to improve the anti diabetic effect of the loaded drug. Glipizide loaded proliposomal  gel was prepared by coacervation-phase separation method using different combinations of drug, sorbitol with cholesterol and lecithin (GF1 – GF6). Proliposome formulations were characterized for physical appearance, pH, vesicle size, entrapment efficiency, drug content uniformity, surface morphology, zeta potential analysis, in-vitro drug release, skin irritation test, and hypoglycemic activity. Among the different formulation, GF2 formulation showed more entrapment efficiency and drug content compared to all other formulations.  The optimized formulation GF4 showed maximum reduction in blood glucose level 101.83 ± 0.983at 24 hrs as compared to oral drug. Proliposomal gel (PLG1) showed no skin irritation and delivered the Glipizide in a controlled manner as compared to conventional dosage form, as evidenced by a significant decrease in blood glucose level in diabetes rats. Thus proliposomal gel will be suitable drug delivery system for Glipizide due to ease of preparation and incorporation of less number of excipients.

Two sensitive and reproducible methods are described for the quantitative determination of Glipizide and Metformin Hydrochloride in presence of its degradation products. The first method was based on high performance liquid chromatographic (LC) separation of the drug from its degradation products on the reversed phase, Cosmosil® column [C18 (5 mm, 4.6 x 150 mm, i.d.)] at ambient temperature using a buffer consisting of 10 mM potassium dihydrogen phosphate (pH adjusted to 2.5 with diluted o- phosphoric acid) and acetonitrile 50: 50 v/v as optimized mobile phase in a gradient program. The flow rate was 0.7 ml min-1 and quantitation was achieved UV determination at 225 nm based on peak area with linear calibration curves at concentration range 10-25 µg ml-1 and 20-50 µg ml-1 respectively. The second method was based on   high performance thin-layer chromatographic (HPTLC) separation followed by densitometric measurement of spots at 216 nm. The separation were carried out on Merck HPTLC aluminium sheets of silica gel 60 F 254 using Toluene: Methanol: Ethyl acetate: Formic acid in the ratio of (3:6:3:0.2, v/v/v/v), as mobile phase. This system was found to give compact spots for Glipizide and Metformin hydrochloride after double development (retention factor, RF 0.08 ± 0.02 and RF 0.74 ± 0.02 respectively). The second order polynomial regression analysis data was used forth regression line in the range of 200-1400 ng spot-1 and 200-1400 ng spot-1 respectively. Both the method has been successively applied to pharmaceutical formulation. No chromatographic interference from the tablet exicipients was found. Both the methods were validated in terms of precision, robustness, recovery, limits of detection and quantitation.

Effective and advantageous Hydrotropic Solubilization technique has been developed for the estimation of two drugs i.e, Flurbiprofen and Glipizide in bulk and its pharmaceutical formulations. Hydrotropic Solubilization technique is one of the aqueous solubility enhancing methods employed for the poorly water soluble drugs and found to be simple, precise and cost effective. Solvents like Piperazine, Urea, Sodium Salicylate, Sodium benzoate etc are the commonly used as hydrotropic solventsin different concentrations. The use of these hydrotropic solvents are of proper choice since the use of organic solvents can be reduced as it is hazardous, costlier and causes environmental pollution. In this context, 1M piperazine has been used as a solubilizing agent to enhance solubility of both the drugs, Flurbiprofen and Glipizide. The absorption maximum of Flurbiprofen and Glipizide was found to be at 246nm and276nm in Zero order derivative spectrum (Method A), calculation of Area Under Curve (AUC)(Method B) was done in the wavelength range of 236-256nm for Flurbiprofen and 266-286nm for Glipizide. The Beer-Lambert’s law has been followed in the concentration range of 2-10µg/ml for Flurbiprofen and 5-35µg/ml for Glipizide for both the methods. The methods were validated as per ICH guidelines and all the validation parameters were found to be within the acceptable range. The developed methods were successfully practiced to estimate the amount of Flurbiprofen and Glipizide in bulk and pharmaceutical dosage forms in routine analysis.

Glipizide is oral hypoglycemic agent, used for treatment of type II diabetes mellitus. Glipizide is insoluble in water. To increase the solubility, dissolution rate and bioavailability of glipizide it must be made its a suitable formulation by incorporating with suitable hydrophilic carriers. Such formulation provides a means of reducing particle size to nearly a molecular level. solid dispersion technique was adapted to enhance the solubility and dissolution rate of glipizide by incorporating hydrophilic carrier such as  Polyvinylpyrrolidone  K30 (PVP-K30) in different ratios were used . The formulation of the solid dispersion were carried our by preparing the  physical mixtures of glipizide using the Polyvinylpyrrolidone  K30 (PVP-K30) in four  different ratios.(1:2, 1:4, 1:6 and 1:8).Characterization of solid dispersions and physical mixtures were confirmed by Determination of Drug content, Solubility study, Thermal study, I R Spectral Analysis, Differential Thermal Analysis (DSC) and Powder x-ray Diffraction Analysis (XRD).From the results it was concluded that the Glipizide : polyvinylpyrrolidone  K30 The dissolution study showed that a maximum increase in dissolution rate was obtained with glipizide: PVP K-30 solid dispersions with a higher ratio of (1:8).

Co-crystals consists of API and a stoichiometric amount of a pharmaceutically acceptable co-crystal former. Pharmaceutical Co-crystals are nonionic supramolecular complexes and can be used to address physical property issues such as solubility, stability and bioavailability in pharmaceutical development without changing the chemical composition of the API. Maximum of the drugs belong to BCS class II, means these are drugs which have low solubility and high permeability. There are various methods of solubility enhancement such as salt formation, solvates, polymorphs, complexation, co-crystallization, etc. Co-crystallization mainly consists of two components the API and the coformer. Thse coformer is the one which acts as a main component for solubility enhancement. In case of ionization or salt formation there is a drawback as compared to co-crystallization. In case, of salt formation or ionization presence of an ionic center is required. This is not a requirement in case of co-crystallization.FDA has approved such combination called Juvisync1 (Sitagliptin and Simvastatin) in 2011.Glipizide belongs to the anti-diabetic class of drug and Rosuvastatin calcium is a cholesterol reducing agent. As both these drugs are class II drug, solubility issues has to be solved. As Glipizide was available not in its salt form, its co-crystallization was decided to do. Hence, co-crystallization method was selected as the method to enhance the solubility. The co-crystals were characterized and showed the conformance of the presence of both the APIs.

The emerging new fixed dose combination of Glipizide (GLZ) as sustained release and Telmisartan (TEL) as immediate release were formulated as a bilayer matrix tablet using guggul. Guggul used as a binding agent with three different concentrations (70%, 80%, and 90%; F1-F6) was used for the preparation of first layer of tablet containing glipizide. The conventional tablet of telmisartan was prepared as a second layer. Prepared bilayer tablets were studied for the in vitro release study carried out at pH 1.2 for first two hours and then at pH 6.8 for 6 hours using USP dissolution apparatus II (Basket). All the evaluation tests were found to be within the acceptance limits specified in Indian Pharmacopeia. The assay and dissolution study of tablets were done by HPLC which was developed and validated according to the ICH Q2 (B) guidelines. The contents of assay of the tablets were found to be 90.92% - 103.84% for F2-F5. The release of glipizide from the tablet was extended up to 8 h. Tablet containing 2.5 mg of glipizide with 80% of guggul release of drug after 8 h was found to be 82.36% and tablet containing 5 mg of glipizide with 90% guggul release of glipizide after 8 h was found to be 74.67%. The release pattern of each formulation (F2-F5) was fitted into the dissolution kinetics models and all the formulations were best fitted in the Higuchi model kinetic. From the results, we have concluded that the guggul act as a binding agent as well as rate retarding agent.

The objective of this study was to develop pH independent immediate release (IR) tablet formulation of Glipizide (GPZ) incorporating β-cyclodextrin (β-CD) and a ternary agent produced by high energy air jet milling complexation technique. GPZ (pKa of 5.9) is poorly water soluble (3.9µgm/ml) exhibiting pH dependent solubility (1.1µgm/ml at pH 2.0 and 26.6 µgm/ml at pH 6.8) owing to which it demonstrates dissolution rate limited absorption and bioavailability. Several complexation techniques involving formation of binary and ternary complexes were evaluated for achieving pH independent release of GPZ. Ternary complex involving GPZ:β-CD: Arginine (1:2:1) prepared using high energy air jet milling was found to be most promising in terms of significant enhancement in solubility, further attaining pH independent dissolution. Molecular modelling (MM) was carried out in order to understand the GPZ:β-CD orientation and GPZ group interactions with the cyclodextrin cavities. Molecular modelling suggested interaction of cyclohexyl and methylpyrazinecarboxamido groups of GPZ with the cyclodextrin cavities and favorability of head to tell (HT) orientation due to its minimum interaction energy. XRD and DSC study showed partial amorphization of GPZ. Scanning electron microscopy (SEM) studies revealed formation of new solid phase of ternary complex indicating partial amorphization. Tablets prepared using optimized ternary complex of GPZ showed immediate and pH independent drug release as compared to marketed tablet formulation and plain drug.