Glimepiride Release Research Articles

Effect of Spray Drying Method on the Properties of Glimepiride-loaded Solid Dispersion

Glimepiride (GLI) is a third-generation sulfonylurea class antidiabetic drug that has low aqueous solubility. The objective of this study was to evaluate the effect of solvents in the development of GLI-loaded solid dispersions (GLISD) using spray drying technique. Two GLI-SD were prepared by adding GLI, polyvinylpyrrolidone (PVP K30), and sodium lauryl sulfate (SLS) in an ethanol/water mixture (solvent evaporation, SE) and water only (surface attached, SA). Intrinsic saturated solubilities and in-vitro dissolution were evaluated and compared to the GLI powder and physical mixture (PM). In addition, physicochemical studies such as scanning electron microscopy, differential scanning calorimetry, and X-ray diffraction were also evaluated. We found that the solubility of GLI was significantly improved by both the preparation methods. The SE method showed 4,960-fold improvement while the SA method displayed 2,900-fold enhancement, which is equivalent to the PM. The in-vitro dissolution studies showed that both methods had a higher release rate, about 1.3-fold for SE and 2-fold for SA, as compared to pure GLI powder. However, GLI release slightly decreased with time for the SA method. Furthermore, solid-state characterizations also revealed that most of the crystalline drug was transformed to the amorphous form in both GLI-SD. Thus, these results indicate that choice of the solvent system plays an important role in the spray drying technique which affects the solubility, dissolution, and crystallinity of poorly soluble drugs such as GLI.

Development and characterization of multiparticulate system as an alternative to unit dosage forms containing drugs with diverse release profiles

BackgroundCurrently, the Bilayer tablets, Tablet in tablet and Inlay tablets composed of Glimepiride (GMP) and Pioglitazone (PGH) as immediate release part, and Metformin (MFH) as sustained-release part are available for the treatment of type II diabetes mellitus (T2DM). In these products, there is a possibility of the incomplete release of immediate release part (GMP and PGH) due to their entrapment into high viscosity gel barrier of MFH sustained-release part when drug product comes in contact with media. Therefore, the present study was aimed to deliver the above combination drugs in the form of hard gelatin capsules (as unit dosage form) containing MFH sustained-release (MFH-SR) pellets and immediate release pellets of PGH and GMP (PG-IR).ResultsThe MFH-SR and GP-IR pellets, prepared by extrusion and spheronization technique, were optimized based on the drug content and % cumulative drug release. The MFH-SR pellets formulation (batch A6) has shown maximum drug content, and sustained-release of MFH similar to marketed glucophage tablet while, the GP-IR pellets formulation (batch B5) has displayed maximum drug contents and immediate release of GMP and PGH; thus, these batches were considered for further characterizations. The optimized MFH-SR and GP-IR formulations have shown particle sizes of 0.23 ± 0.0010 mm and 0.35 ± 0.0018 mm, respectively. Besides, the formulations exhibited good micromeritics properties. The in vivo pharmacokinetic study in rabbits has demonstrated comparable bioavailability of the drugs from pellets and the marketed formulations following oral administration. Further, the pellets were found to be stable for 6 months at 40 ± 2 °C/75% ± 5%RH.ConclusionsThe study results revealed that the multiparticulate systems with varied release profiles could be a promising approach to overcome drug release issues associated with the unit dosage forms.

Synthesis and characterization of mesoporous silica and its application as drug delivery system for glimepiride.

The objective of this study was to synthesize the mesoporous silicate SBA-15 loaded with glimeperide, a slightly soluble antidiabetic, and to investigate the impact of drug loading on the release of glimepiride from this carrier. SBA-15 mesospheres were synthesized by addition of HCl to the trico-polymer (PEO20PPO70PEO20) until complete dissolution, then by addition of tetraethyl orthosilicate, stirring and drying until mesospheres powder was received. The mesopheres were characterized by thermal gravimetric analysis, powder X-ray diffraction, and Fourier transfer infrared analysis. The morphology was examined under a Scanning Electron Microscope. The surface area of the prepared mesospheres was determined by Brunauer-Emmett-Teller and the compression behavior of the powder was also studied. Then glimepiride was loaded on the mesospheres and percent loading as well as drug release was studied. Results showed successful preparation of the mesospheres with a glimepiride loading of was 40% with significant release improvement of glimepiride dissolution. A proportion of 70% glimepiride was released in the first 10 min compared to 5 % pure drug. It was concluded that the prepared mesospheres highly improve dissolution of glimeperide.

BIOWAIVER STUDY OF IMMEDIATE RELEASE GLIMEPIRIDE TABLETS

Objective: Demonstrating therapeutic equivalency regarding the efficacy and safety among originator products and generics is a key step in permitting the marketing of generic products. The study aimed to evaluate the bioequivalence of five different generic brands of Glimepiride tablets under biowaiver conditions.
 Methods: The quality of the tablet products, including uniformity of weight, friability, and disintegration test, was assessed using the United State Pharmacopeia (USP) general monograph for the tablet dosage form. The content of glimepiride in the tablets was measured using UV spectrophotometer at the wavelength 229 nm. The release of Glimepiride from the tested and originator tablet products was evaluated using the dissolution profiles conducted in HCI buffer pH 1.2, and phosphate buffer pH 6.4 and 7.8 by USP dissolution apparatus II. The bioequivalence of test products was assessed using the similarity and difference factors. 
 Results:The tested products complied to USP requirements for quality standards; all the products show rapid disintegration, D1 show higher time (Three minutes) while D3 show lower time (28 seconds). The content of test products was (104.68, 93.75, 97.21, 97.03, and 102.10) for D1, D2, D3, D4, and D5 , respectively, compare to 103.70 for OB. Dissolution profiles revealed that the highest similarity to the originator was showed in pH 6.4; f2 ranged (74.5-68.4) for all the tested products and low similarity in pH 7.8; f2 ranged (45.2-64.7).
 Conclusion: The study showed that the generic products has noticeable similarity with the originator brand and it can be interchangeable.

Development and Evaluation of Gastrobioadhesive Glimepiride Sustained Release Matrix Tablet Using Aegle Marmelos Polysaccharide

The purpose of present study was to formulate and evaluate glimepiride gastrobioadhesive drug delivery using Aegle Marmelos polysaccharide and synthetic polymer for prolongation of gastric residence time and reduce the dosing frequency. Glimepiride matrices were prepared by direct compression method and evaluated with an aim of presenting glimepiride as sustained release for improving the patient’s compliance. A central composite design (CCD) was employed as Aegle Marmelos polysaccharide (X1) and HPMC K4M (X2) independent variables to optimize the glimepiride in terms of sustained release and gastrobioadhesive. The response (Y1) as bioadhesive strength, (Y2) percentage drug releases at 8 h and (Y3) time (t50) required to 50% drug release were measured for each trial and statistical equations with significant interaction terms were derived to predict relation. The physical properties of all formulations hardness, friability, drug content and weight variation were found within limits indicating that the prepared matrix tablets met the USP specifications. Among all the formulations, F1 formulation found to be optimized based on the criteria of attaining the maximum value of drug released Q8 of 98.58±1.12%, 18.43 g bioadhesive strength and time to 50% drug release (t50) of 6 h. An in-vitro drug release studies reveals that as concentrations of polymers increases the drug release decreases, producing sustained release of glimepiride. The release co-efficient values ‘n’ (˂0.3645) indicated that the drug release (F1) followed fickian diffusion mechanism kinetics. A glimepiride gastroadhesive matrix was developed to enhance its bioavailability by prolonging the gastric residence time with desirable release modulation for a once daily administration.

Preparation and evaluation of porosity osmotic pump tablets for sustain release of Glimepiride

Preparation and evaluation of porosity osmotic pump tablets for sustain release of Glimepiride

Effect of coating method on release of Glimepiride from porosity osmotic pump tablets (POPTs)

In this study, once-daily porosity osmotic pump tablets (POPTs) of Glimepiride were prepared using HPMC K100M (61%), osmotic agent (30% NaCl) coated using two different coating techniques spraying and dipping methods. The coating solution composed of ethyl
 
 cellulose (7.5%) w\w in ethanol (90%), castor oil (2%) as water-insoluble plasticizer and Gingo red color (0.5% w\w). In both techniques, the coating level was adjusted to give a 10% increase in the weight of the tablets. The effect of the coating by dipping technique with an increase in the weight of tablet (10 %, 20% & 50%) was also investigated to see the effect coating level on the percentage of drug release from POPTs.
 The results of the in vitro release of Glimepiride from tablets coated by the spraying method showed longer release time (24 hrs) than those coated with dipping method. On the other hand, increasing the coating level by dipping method retarded the release of the drug from tablets. However, the same retardation effect on release as shown with the spraying technique was only obtained by increasing the coating level with a 50% increase in the weight of the tablet. Thus, coating by spraying is more efficient to prepare POPTs to give a continuous release of Glimepiride from once daily table with the lowest increase in the total weight of the tablet.

Effect of coating method on release of Glimepiride from porosity osmotic pump tablets (POPTs)

In this study, once-daily porosity osmotic pump tablets (POPTs) of Glimepiride were prepared using HPMC K100M (61%), osmotic agent (30% NaCl) coated using two different coating techniques spraying and dipping methods. The coating solution composed of ethyl cellulose (7.5%) w\w in ethanol (90%), castor oil (2%) as water-insoluble plasticizer and Gingo red color (0.5% w\w). In both techniques, the coating level was adjusted to give a 10% increase in the weight of the tablets. The effect of the coating by dipping technique with an increase in the weight of tablet (10 %, 20% & 50%) was also investigated to see the effect coating level on the percentage of drug release from POPTs. The results of the in vitro release of Glimepiride from tablets coated by the spraying method showed longer release time (24 hrs) than those coated with dipping method. On the other hand, increasing the coating level by dipping method retarded the release of the drug from tablets. However, the same retardation effect on release as shown with the spraying technique was only obtained by increasing the coating level with a 50% increase in the weight of the tablet. Thus, coating by spraying is more efficient to prepare POPTs to give a continuous release of Glimepiride from once daily table with the lowest increase in the total weight of the tablet.

Formulation and In Vitro Evaluation of Bilayered Matrix Tablets of Pioglitazone for Immediate Release and Glimepiride for Extended Release

Bi-layer tablets are novel drug delivery systems where a combination of two or more drugs in a single unit having different release profiles which improves patient compliance and prolongs the drug action. The study was performed to design bilayer matrix tablets of pioglitazone for immediate release and glimepiride for extended release delivery system. Bilayered matrix tablets composed of two layers, one is immediate release and a second layer is extended release layers. The immediate release layer comprised sodium starch glycolate, and croscarmellose sodium as super disintegrates and extended release layer comprised ethyl cellulose and HPMC K4M as release retardant polymers. Direct compression method was employed for the formulation of bilayer tablets. In vitro studies have shown more than 80% of pioglitazone was released within 60 min. Ethyl cellulose and HPMC K4M retarded the release of glimepiride from the controlled release layer for 12 h. Drug release mechanism exponent (n) was determined for all formulations (0.689-0.789). The release of pioglitazone was found to follow a first order release and the release of glimepiride was followed zero order release model.

Development and Evaluation of Novel Tabletted Microspheres for Controlled Release of Glimepiride

Development and Evaluation of Novel Tabletted Microspheres for Controlled Release of Glimepiride

Design of Gastroretentive Floating Bilayer Tablets of Metformin and Glimepiride

The present study involves designing and development of a bilayer tablet of Metformin HCl (MET) and Glimepiride (GLP) to offer immediate release of GLP and gastroretentive layer of MET. Bilayer tablets containing two layers i.e. immediate release layer formulated using super disintegrant Sodium starch glycolate and gastroretentive layer formulated with polymers like HPMC K4M and HPMC K100M to modulate the biphasic drug release. Wet granulation method was employed to formulate bilayer tablets. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM) were used for physicochemical compatibility and stability studies of the tablets. Accelerated stability studies were followed in compliance with ICH guidelines. The in vitro release profile shows desired biphasic release behavior after storage at accelerated condition (40°C± 2°C and 75%RH ± 5% RH) for 6 months. Biphasic drug release pattern was successfully achieved through the formulation of bilayer tablets that are stable and capable of releasing the drug over 12 hrs.

Enhanced transdermal controlled delivery of glimepiride from the ethylene-vinyl acetate matrix

An ethylene-vinyl acetate (EVA) matrix containing glimepiride was prepared as a potential transdermal drug delivery system. Permeation studies of quinupramine through the EVA copolymer membrane were carried out using a two-chamber diffusion cell. The rate of drug permeation through the EVA membrane was proportional to the PEG 400 volume fraction. The release of glimepiride from the EVA matrix was examined using a modified Franz diffusion cell. A plasticizer was added to prepare the pore structure of the EVA matrix in order to increase the rate of drug release. The effects of PEG 400, drug concentration, temperature, and plasticizer on the drug release rate were investigated. Various types of enhancers were added to an EVA matrix containing 2% glimepiride in an attempt to increase the level of skin permeation of quinupramine through an EVA matrix. The effects of the enhancers on the level of glimepiride permeation through the skin were evaluated using Franz diffusion cells fitted with intact excised rat skin. The rate of drug release from the EVA matrix increased with increasing PEG 400 volume fraction, temperature, and drug loading. The estimated activation energy of drug release was 7.274 kcal/mol for 2% drug loading dose. The release of glimepiride from the EVA matrix followed a diffusion-controlled model, where the quantity released per unit area was proportional to the square root of time. The controlled release of glimepiride was achieved using the EVA polymer including the plasticizer. Among the plasticizers used, such as the alkyl citrates and phthalates groups, diethyl phthalate slightly increased the rate of glimepiride release. Among the various enhancers used, such as the non-ionic surfactants, the glycerides, the propylene glycol derivatives, fatty acids (saturated or unsaturated), and pyrrolidones, linoleic acid showed the highest permeation rate; 3.17-times higher than the control. In conclusion, an EVA matrix containing a permeation enhancer can be used for the transdermal controlled delivery of glimepiride.

아마릴 정(글리메피리드 2mg)에 대한 글리메드 정의 생물학적 동등성

The purpose of the present study was to evaluate the bioequivalence of two glimepiride tablets, (Handok/Aventis Pharm. Co., Ltd.) and Glimed (Kuhn II Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The glimepiride release from the two glimepiride formulations in vitro was tested using KP VIII Apparatus II method with a variety of dissolution media (pH 1.2, 4.0, 6.8 buffer solution, water and blend of PSB 80 into each dissolution medium). Twenty six healthy male subjects, years in age and kg in body weight, were divided into two groups and a randomized cross-over study was employed. After one tablet containing 2 mg as glimepiride was orally administered, blood was taken at predetermined time intervals and the concentrations of glimepiride in serum were determined using HPLC method with UV detector. The dissolution profiles of two formulations were similar at all dissolution media. Besides, the pharmacokinetic parameters such as , and were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed , and untransformed . The results showed that the differences between two formulations based on the Amaryl were -3.70, -8.28 and 0.61% for , and , respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) (e.g., for for and , respectively). Thus, the criteria of the KFDA guideline for the bioequivalence were satisfied, indicating Glimed tablet and Amaryl tablet were bioequivalent.