Formulation and Evaluation of Immediate Release Tablets of Glimepiride Solid Dispersion

Poor aqueous solubility remains one of the major challenges in the development of oral pharmaceutical formulations. Nearly 40–70% of newly discovered drug molecules exhibit poor water solubility, resulting in slow dissolution, reduced gastrointestinal absorption, and low oral bioavailability. Consequently, enhancing the dissolution behavior of poorly soluble drugs has become an important objective in pharmaceutical research.¹˒²

Glimepiride is a third-generation sulfonylurea antidiabetic agent widely prescribed for the treatment of Type 2 Diabetes Mellitus. Although it exhibits excellent hypoglycemic activity, its therapeutic performance is limited by poor aqueous solubility and dissolution rate. As a Biopharmaceutical Classification System (BCS) Class II drug, glimepiride possesses high permeability but low solubility, making dissolution the rate-limiting step for its oral absorption.³˒⁴

Several formulation strategies have been investigated to improve the dissolution characteristics of poorly soluble drugs, including micronization, salt formation, complexation, nanotechnology, lipid-based drug delivery systems, and solid dispersion technology. Among these approaches, solid dispersion is considered one of the most effective, economical, and industrially feasible techniques for enhancing drug solubility and dissolution.⁵˒⁶

Solid dispersion is defined as the dispersion of one or more active pharmaceutical ingredients within an inert hydrophilic carrier in the solid state. This technique improves drug dissolution through particle size reduction, enhanced wettability, increased porosity, and conversion of the crystalline drug into an amorphous or partially amorphous form. Hydrophilic carriers promote rapid water penetration and facilitate faster drug release, thereby improving oral bioavailability.⁷˒⁹

Solid dispersions can be prepared using several techniques such as fusion, solvent evaporation, kneading, hot-melt extrusion, spray drying, co-precipitation, and lyophilization. Among these methods, the solvent evaporation technique is widely preferred because it minimizes thermal degradation and produces homogeneous molecular dispersion of the drug within the carrier matrix.⁸˒¹⁰

Immediate release tablets are designed to disintegrate rapidly after oral administration and release the drug without any intentional delay. Such formulations provide faster onset of therapeutic action, improved patient compliance, and enhanced drug absorption. The combination of optimized solid dispersion with immediate release tablet technology represents a promising approach for improving the dissolution profile of poorly soluble drugs such as glimepiride.¹¹˒¹³

In the present investigation, solid dispersions of glimepiride were prepared using different techniques and carriers to enhance drug solubility and dissolution. The optimized solid dispersion prepared by the solvent evaporation method was incorporated into immediate release tablets and evaluated for pre-compression parameters, post-compression characteristics, and in vitro dissolution performance. The developed formulation was expected to provide improved pharmaceutical performance and enhanced oral bioavailability compared with the pure drug

MATERIALS AND METHODS

Materials

Glimepiride was used as the model drug for the preparation of immediate release tablets. Sodium starch glycolate, lactose monohydrate, microcrystalline cellulose (MCC), starch, polyvinyl pyrrolidone (PVP K-30), talc, and magnesium stearate were used as pharmaceutical excipients. All chemicals and reagents used in the study were of analytical grade.

Instruments

The study was carried out using a Rimek Mini Press tablet compression machine, Pfizer hardness tester, Roche friabilator, USP disintegration test apparatus, Lab India DS 8000 dissolution test apparatus, Shimadzu FTIR spectrophotometer, Shimadzu DSC-60 differential scanning calorimeter, UV–Visible spectrophotometer (Lab India UV-3200), electronic analytical balance, and Vernier calipers for tablet evaluation.

Preformulation Studies

Preformulation studies were performed to characterize glimepiride before formulation development. The drug was evaluated for λmax determination, calibration curve, melting point, saturation solubility, Fourier Transform Infrared (FTIR) spectroscopy, and Differential Scanning Calorimetry (DSC). λmax was determined by UV spectroscopy after preparing suitable dilutions of glimepiride in phosphate buffer (pH 7.8), while the calibration curve was constructed over the concentration range of 5–30 µg/mL. Drug–excipient compatibility was investigated using FTIR and DSC analysis.

Preparation of Solid Dispersions

Solid dispersions of glimepiride were prepared using four different techniques, namely physical mixing, kneading, solvent evaporation, and fusion method. Different drug-to-polymer ratios (1:0.5, 1:1, and 1:1.5) were prepared for each technique. In the solvent evaporation method, glimepiride and sodium starch glycolate were dissolved in methanol, followed by evaporation of the solvent under reduced pressure. The dried mass was pulverized, passed through sieve no. 100, and stored in a desiccator until further use.

Evaluation of Solid Dispersions

Prepared solid dispersions were evaluated for drug content, entrapment efficiency, and in vitro dissolution. Drug content was determined spectrophotometrically at 228 nm using phosphate buffer (pH 7.8). Entrapment efficiency was calculated as the percentage ratio of drug content to the theoretical drug content. Dissolution studies were carried out using USP Apparatus II (Paddle) containing 900 mL phosphate buffer (pH 7.8) maintained at 37 ± 0.5°C and stirred at 50 rpm. Samples were withdrawn at predetermined intervals and analyzed at 228 nm.

Formulation of Immediate Release Tablets

The optimized solid dispersion was selected for the preparation of immediate release tablets by direct compression. All ingredients were passed through a 60-mesh sieve and blended uniformly. Talc and magnesium stearate were incorporated as lubricant and glidant, respectively. Tablets containing an equivalent of 4 mg glimepiride were compressed using a Rimek Mini Press equipped with a 9 mm punch. The average tablet weight was maintained at 200 mg, while tablet hardness was adjusted between 3–4 kg/cm².

Evaluation of Immediate Release Tablets

Prepared tablets were evaluated for pre-compression parameters including bulk density, tapped density, angle of repose, Carr's compressibility index, and Hausner ratio. Post-compression evaluation included hardness, friability, weight variation, thickness, drug content uniformity, disintegration time, and in vitro dissolution study according to pharmacopeial procedures. Dissolution testing was performed using USP Apparatus II in 900 mL phosphate buffer (pH 7.8) at 37 ± 0.5°C and 50 rpm. Drug release was quantified spectrophotometrically at 228 nm.

RESULTS AND DISCUSSION

Determination of λ Max and Calibration Curve - The standard stock solution was prepared as per the method described in experimental section and scanned by UV-Visible spectrophotometer. The UV absorption spectrum of Glimepiride showed peak at 228 nm.

 

Fig 1: UV Spectrum of Glimepiride.

 

Fig 2: Calibration curve of Glimepiride

 

Fig 3: Solubility studies of Glimepiride

 

Fig 4: IR spectrum of pure Glimepiride

 

Fig 5: IR spectrum of physical mixture of drug and excipient blend

 

Fig 6: DSC thermo gram of Drug: Excipient Blend

Table 11: In-Vitro drug release studies for formulations (PF1-PF3)

Time(min)	1:0.5 (PF1)	1:1(PF2)	1:1.5 (PF3)
0	0	0	0
5	25.47	28.06	29.35
15	39.84	42.44	43.74
30	50.26	51.57	54.16
45	61.96	65.85	67.15
60	72.37	74.98	77.57
75	81.48	85.37	86.68
90	91.87	94.48	95.78

 

 

Fig 7: In-Vitro drug release profile for Glimepiride: Sodium starch glycolate (PF1-PF3)

Table 12: In-Vitro drug release studies for formulations (KF1-KF3)

Time(min)	1:0.5 (KF1)	1:1(KF2)	1:1.5 (KF3)
0	0	0	0
5	26.77	29.35	30.65
15	43.73	43.74	43.75
30	51.58	55.46	54.16
45	65.85	68.45	68.45
60	76.27	78.87	77.58
75	85.38	87.98	89.27
90	94.48	97.08	98.38

 

 

Fig 8: In-Vitro drug release profile for Glimepiride: Sodium starch glycolate (KF1-KF3)

 

Fig 9: In-Vitro drug release profile for Glimepiride: Sodium starch glycolate (SF1-SF3)

Table 7.14: In-Vitro drug release studies for formulations (FF1-FF3)

Time(min)	1:0.5 (F1)	1:1(F2)	1:1.5 (F3)
0	0	0	0
5	26.77	28.06	29.35
15	39.85	42.44	43.74
30	51.56	52.86	54.16
45	61.97	65.85	68.45
60	73.66	76.27	78.87
75	81.48	85.38	87.98
90	93.17	95.77	97.08

 

 

Fig 10: In-Vitro drug release profile for Glimepiride: Sodium starch glycolate  (FF1-FF3)

Table 18: % Cumulative drug release of formulations F1-F6

Time(Min)	F1	F2	F3	F4	F5	F6
00	0	0	0	0	0	0
05	39.70	37.11	37.11	33.23	34.53	33.23
10	52.85	50.25	48.96	50.23	47.65	45.06
15	67.15	64.55	63.24	63.25	60.65	63.22
20	80.16	76.26	76.26	74.96	74.95	74.96
25	91.87	90.55	86.67	89.25	86.66	84.08
30	99.69	97.10	95.78	97.09	95.78	94.47

 

 

Fig 11:  In-Vitro Drug Release of F1-F3

 

Fig 12:  In-Vitro Drug Release of F4-F6

Discussion:

The complete comparative study of 200 mg various tablets for the equivalent weight of Glimepiride 04 mg various tablets formulated by Glimepiride solid dispersion with excipients. The rate of dissolution was excellently increased that tablets which were formulated from solid dispersions with excipients. Moreover formulation F1 showed their highest release (99.69%) for the tablets formed by solid dispersion 1:1.5(Glimepiride: Sodium starch glycolate) with MCC (86mg).

CONCLUSION

Sodium starch glycolatewas used in the preparation of solid dispersions by physical mixture method, kneading method, solvent evaporation and Fusion method.

Formulation (SF3) containing Glimepiride +  Sodium starch glycolate(1:1.5) shows better results by solvent evaporation method at the end of 90 min with drug release of 99.68 %, hence it was selected as the best formulation.  In this study, it was found that use of disintegrating agent as carrier for solid dispersions is a suitable technology to improve the dissolution behavior of poorly water soluble drugs.

In this study, it was found that the tablets prepared with the lactose, MCC and starch as diluents, tablets with lactose and MCC combination tend to exhibit rapid dissolution. The rate of drug release is (lactose +MCC) > (lactose + starch) in the tablet formulations.

Moreover formulation F1 showed their highest release (99.69%) for the tablets formed by solid dispersion 1:1.5(Glimepiride: Sodium starch glycolate) with MCC (86mg) as diluent.

SUMMARY

Glimepiride is a poorly water-soluble antidiabetic drug whose oral performance is limited by slow dissolution. The present study investigated the preparation of glimepiride solid dispersions using sodium starch glycolate by physical mixing, kneading, solvent evaporation and fusion methods in different drug-to-carrier ratios (1:0.5, 1:1 and 1:1.5). The prepared formulations were evaluated for drug content, entrapment efficiency, compatibility and in-vitro drug release. Among all formulations, SF3 prepared by the solvent evaporation method (1:1.5) exhibited the best performance with 99.68% drug release after 90 minutes, together with excellent drug content and entrapment efficiency. The optimized solid dispersion was further formulated into immediate-release tablets. All tablet formulations satisfied pharmacopeial quality requirements, while formulation F1 containing MCC as diluent demonstrated the highest drug content (99.59%) and drug release (99.69%). The findings indicate that sodium starch glycolate-based solid dispersion prepared by solvent evaporation is an effective strategy for enhancing the dissolution of glimepiride and is a promising approach for developing immediate-release oral dosage forms.

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