Development and Evaluation of Ticagrelor Solid Dispersion Tablets Using PVP K30, PEG 6000 and HPMC E5 for Dissolution Enhancement

Soni Bansod; Prof. Vinayak Mundhe

Department of Pharmaceutics, Dr. Vedprakash Patil Pharmacy College, Chh. Sambhajinagar

*Correspondence: maparimangesh42@gmail.com

DOI: https://doi.org/10.71431/IJRPAS.2026.5716            

INTRODUCTION:

Oral drug delivery continues to be the most preferred route of drug administration because of its convenience, patient acceptability, cost-effectiveness and suitability for chronic therapy. However, successful oral delivery depends strongly on the aqueous solubility and permeability of the active pharmaceutical ingredient. A large proportion of modern drug candidates show high lipophilicity and poor water solubility, which results in slow dissolution in gastrointestinal fluids and consequently low or variable oral bioavailability [1-3].

The Biopharmaceutics Classification System classifies drugs according to solubility and permeability. BCS Class IV drugs are especially challenging because they combine low aqueous solubility with low permeability. For such drugs, improvement of dissolution can be a critical first step toward enhancing oral absorption, even though permeability barriers may still remain [4,5]. Ticagrelor is a cyclopentyl-triazolo-pyrimidine antiplatelet agent and a reversible P2Y12 adenosine diphosphate receptor antagonist. It is used to prevent thrombotic cardiovascular events in patients with acute coronary syndrome. Despite its clinical importance, ticagrelor exhibits poor aqueous solubility and variable oral absorption, which can influence the consistency of antiplatelet response [6-10].

Several pharmaceutical approaches have been investigated to improve the dissolution and bioavailability of poorly soluble drugs, including micronization, complexation, lipid-based delivery systems, salt formation and solid dispersion technology. Among these approaches, solid dispersion has attracted considerable attention because the drug may be molecularly dispersed or distributed in an amorphous state within a hydrophilic carrier matrix. This can enhance wettability, increase effective surface area, reduce crystal lattice energy and generate supersaturation during dissolution [11-15]. Hydrophilic polymers such as PVP K30, PEG 6000, HPMC and poloxamers are widely used because they improve drug wetting and can inhibit recrystallization of the amorphous drug [16-20].

Although solid dispersion improves dissolution at the powder level, its conversion into a practical tablet dosage form is necessary for patient use and industrial relevance. Tablets offer dose accuracy, ease of handling, portability, stability and large-scale manufacturability. The present work therefore focused on the formulation and evaluation of ticagrelor solid dispersion tablets using simple and cost-effective hydrophilic carriers, with the objective of improving dissolution performance while maintaining acceptable tablet quality attributes.

MATERIALS AND METHODS

Materials

Ticagrelor was obtained from Mehta Chemical. PVP K30, PEG 6000 and HPMC E5 were obtained from Loba Chemie Pvt. Ltd., India. Microcrystalline cellulose was used as diluent and compression aid. Sodium starch glycolate was used as superdisintegrant, while magnesium stearate and talc were used as lubricant and glidant, respectively. Methanol/ethanol and distilled water were used as analytical and formulation solvents. All chemicals and excipients were of pharmaceutical or analytical grade.

Preformulation studies

Ticagrelor was evaluated for organoleptic properties, solubility, melting point and UV spectrophotometric characteristics. Organoleptic properties were observed visually under daylight. Solubility was studied in distilled water, phosphate buffer pH 6.8, methanol, ethanol, 1 N hydrochloric acid, chloroform and DMSO by adding excess drug to each solvent, shaking for 24 h, filtering and observing clarity. Melting point was determined by the capillary tube method and compared with literature values.

For UV analysis, 10 mg ticagrelor was dissolved and diluted to prepare a stock solution of 100 µg/mL. A working solution was scanned from 200 to 400 nm against solvent blank to determine λmax. Calibration standards of 2, 4, 6, 8 and 10 µg/mL were analyzed at 255 nm, and linear regression was used to obtain the analytical equation.

Drug-excipient compatibility studies

FTIR studies were performed by scanning pure ticagrelor and drug-excipient physical mixtures in the range of 4000-400 cm-1. Characteristic peaks were compared to evaluate possible chemical interactions. Differential scanning calorimetry was performed for pure drug and physical mixture samples by heating sealed aluminum pans from 30 °C to 300 °C at 10 °C/min under nitrogen atmosphere. Any changes in peak temperature, intensity or shape were interpreted for thermal compatibility.

Preparation of ticagrelor solid dispersion tablets

Ticagrelor solid dispersions were prepared by solvent evaporation and compressed into tablets by direct compression. Accurately weighed quantities of ticagrelor, PVP K30, PEG 6000 and HPMC E5 were dissolved or dispersed in a minimum quantity of volatile solvent with continuous stirring to obtain a homogeneous system. The solvent was evaporated in a hot air oven at approximately 40-45 °C until a dry mass was obtained. The dried mass was scraped, triturated and passed through sieve no. 60. The solid dispersion equivalent to 60 mg ticagrelor was blended with MCC and sodium starch glycolate, followed by final lubrication with magnesium stearate and talc. The final blend was evaluated and compressed into 300 mg tablets.

Table 1. Key formulation variables of ticagrelor solid dispersion tablets.

Evaluation of powder blend and tablets

Powder blends were evaluated for bulk density, tapped density, angle of repose, Carr’s index and Hausner ratio using standard procedures. Compressed tablets were evaluated for physical appearance, average weight, thickness, hardness, friability, drug content, disintegration time and in-vitro dissolution. Drug content was determined after powdering tablets, dissolving an equivalent quantity in solvent, filtering and measuring absorbance at 255 nm. Dissolution testing was performed using phosphate buffer pH 6.8 as dissolution medium at 37 ± 0.5 °C. Samples were withdrawn at predetermined time points and analyzed by UV spectrophotometry.

Stability study

The optimized batch was packed in suitable containers and stored under accelerated conditions of 40 ± 2 °C/75 ± 5% RH for three months. Samples were withdrawn at one-month intervals and evaluated for physical appearance, thickness, hardness, friability, drug content, disintegration time and final drug release.

RESULTS AND DISCUSSION

Preformulation and analytical method

Ticagrelor was observed as a white to off-white crystalline, odorless powder with slightly bitter taste. It was practically insoluble in water and phosphate buffer pH 6.8 but showed better solubility in organic solvents, confirming the need for dissolution-enhancement technology. The melting point was 144.75 °C, showing a sharp thermal transition consistent with crystalline drug purity. The UV spectrum showed maximum absorbance at 255 nm in methanol. Calibration data followed Beer-Lambert’s law over 2-10 µg/mL with the regression equation A = 0.0614C - 0.0186 and R² = 0.9959, confirming the suitability of the method for drug content and dissolution analysis.

Table A1. Actual UV calibration curve data of ticagrelor from thesis.

Figure 1. Actual UV absorption maximum of ticagrelor

The UV data show a linear increase in absorbance from 0.113 to 0.602 over 2-10 µg/mL. The original thesis figure confirms the absorption maximum of ticagrelor around 255 nm.

Figure 2. Calibration curve of ticagrelor at 255 nm.

FTIR and DSC compatibility assessment

The FTIR spectrum of ticagrelor showed characteristic peaks corresponding to hydroxyl, aromatic C-H, carbonyl, aromatic C=C and ether functional groups. The key peaks were retained in the drug-excipient mixture, suggesting absence of major chemical interaction. DSC analysis of pure ticagrelor showed a sharp endothermic peak at 144.75 °C, indicating crystalline nature. In the physical mixture, a broad peak was observed at 139.45 °C with reduced intensity. The slight shift and broadening may be attributed to dilution and interaction with polymeric carriers; however, retention of the endothermic event indicated compatibility of ticagrelor with the selected excipients.

Figure 3. Actual FTIR spectra from thesis: pure ticagrelor and ticagrelor with excipients.

The FTIR data retain characteristic peaks for O-H stretching, aromatic C-H stretching, C=O stretching, aromatic C=C stretching and ether linkages. Retention of these bands in the mixture supports drug-excipient compatibility.

Table 2. Characteristic FTIR peaks of ticagrelor.

Figure 4. Actual DSC thermograms from thesis: pure ticagrelor and ticagrelor with excipients.

Pure ticagrelor shows a sharp endothermic peak at 144.75°C, while the physical mixture shows a broadened peak at 139.45°C. The drug peak is retained with slight shift and reduced enthalpy, indicating compatibility with the selected excipients.

Table 3. DSC interpretation of ticagrelor and physical mixture.

Figure 5. DoE contour and 3D surface plots for disintegration time

Figure 6. DoE contour and 3D surface plots for drug release after 8 h

The actual DoE results show that batch F6, containing 60 mg PVP K30 and 60 mg PEG 6000, produced the highest drug release (83%) with a comparatively lower disintegration time of 45 min. This response region is visible in the original DoE contour and surface plots.

3.3 Powder blend characteristics

Precompression evaluation indicated that all formulations possessed acceptable flow and compressibility for direct compression. Angle of repose values ranged from 27.4° to 31.5°, indicating good to excellent flow. Carr’s index values ranged from 11.53% to 17.64%, while Hausner ratios ranged from 1.13 to 1.21. Batch F6 showed the best micromeritic profile with an angle of repose of 27.4°, Carr’s index of 11.53% and Hausner ratio of 1.13, suggesting excellent flow and packing behavior. These values are important because uniform die filling during compression directly influences tablet weight uniformity and content uniformity.

Table 4. Precompression evaluation of ticagrelor solid dispersion powder blends.

Post-compression evaluation

All prepared tablets were physically acceptable and showed satisfactory tablet quality characteristics. Weight values ranged from 290 to 306 mg, suggesting acceptable manufacturing uniformity around the target weight of 300 mg. Thickness values ranged from 1.5 to 2.9 mm and reflected differences in polymer concentration, powder packing and compression behavior. Hardness ranged from 1.7 to 3.2 kg/cm², and batch F6 showed the highest hardness of 3.2 kg/cm², indicating superior compact integrity. Friability values were below 1% for all batches, ranging from 0.41% to 0.74%, confirming adequate resistance to abrasion and mechanical stress. Drug content ranged from 96.4% to 99.4%, showing uniform drug distribution within the formulations.

Table 5. Post-compression evaluation and final drug release of ticagrelor tablets.

In-vitro disintegration and dissolution behavior

Disintegration time ranged from 40 to 90 min and was influenced by the relative levels of PVP K30, PEG 6000 and MCC. Higher polymer content improved wettability but could also influence matrix hydration and tablet breakup. Although F7 showed the shortest disintegration time of 40 min, it did not produce the highest drug release. The optimized F6 batch showed an acceptable disintegration time of 45 min and the highest final cumulative drug release of 83%. This suggests that an appropriate balance between hydrophilic carrier concentration, matrix structure and tablet mechanical integrity is necessary for improved release.

The dissolution profiles confirmed that solid dispersion improved drug release compared with formulations containing lower or unbalanced polymer ratios. Batch F6 showed faster and more complete release throughout the dissolution period, reaching 83% at the final sampling point. The enhanced release may be attributed to improved wetting by PVP K30 and PEG 6000, partial amorphization or reduced crystallinity, increased dispersion of ticagrelor within the polymeric carrier and rapid penetration of dissolution medium into the matrix. Formulations F2, F3 and F8 showed lower final release (65%), suggesting that simply increasing PEG 6000 without an optimized carrier-diluent balance did not maximize release.

Figure 7. In-vitro dissolution profiles of ticagrelor solid dispersion tablets.

Figure 8. Final drug release of formulations F1-F9.

Optimization of formulation

The overall evaluation identified F6 as the optimized formulation. F6 contained 60 mg ticagrelor, 60 mg PVP K30, 60 mg PEG 6000, 30 mg HPMC E5, 70 mg MCC, 10 mg sodium starch glycolate, 5 mg magnesium stearate and 5 mg talc per 300 mg tablet. This batch showed the most balanced profile across precompression, mechanical and dissolution parameters. PVP K30 acted as a hydrophilic carrier and possible crystallization inhibitor, while PEG 6000 improved wettability and drug dispersion. HPMC E5 contributed to formulation stability and matrix integrity. The optimization results support the selection of intermediate PVP K30 with higher PEG 6000 concentration and adequate MCC content as an effective combination for ticagrelor solid dispersion tablets.

Table 6. Composition of optimized batch F6.

Stability of optimized batch

The optimized F6 tablets remained physically stable during three months of accelerated stability testing. No change in appearance was observed. Thickness remained constant at 2.3 mm, while hardness decreased slightly from 3.2 to 3.0 kg/cm² and friability increased from 0.41% to 0.47%, remaining within acceptable limits. Drug content decreased slightly from 99.4% to 98.5%, and final drug release decreased from 83% to 80%. The modest changes may be due to polymer hydration or gradual structural relaxation during storage, but the formulation remained pharmaceutically acceptable over the study period.

Table 7. Stability study results for optimized batch F6.

Figure 9. Stability trend of optimized batch F6 over three months.

CONCLUSION

Ticagrelor solid dispersion tablets were successfully prepared using PVP K30, PEG 6000 and HPMC E5 by solvent evaporation followed by direct compression. Preformulation studies confirmed the poor aqueous solubility and crystalline nature of ticagrelor, justifying the use of solid dispersion technology. FTIR and DSC studies indicated compatibility between ticagrelor and selected excipients. Prepared powder blends showed acceptable to excellent flow properties, and the compressed tablets met important quality requirements such as uniform weight, acceptable friability and satisfactory drug content. Among the nine batches, F6 exhibited the best overall performance with excellent flow, highest hardness, lowest friability, acceptable disintegration, highest drug content and maximum final drug release. Stability results showed that the optimized formulation remained stable under accelerated conditions for three months with only minor changes in quality attributes. Overall, the study demonstrates that a simple hydrophilic polymer-based solid dispersion approach can improve the dissolution performance of ticagrelor and can be further investigated for scale-up and in-vivo bioavailability enhancement.

FUTURE SCOPE

Future studies should include solid-state characterization of the optimized formulation by powder X-ray diffraction and scanning electron microscopy to confirm amorphization and surface morphology. In-vivo pharmacokinetic and pharmacodynamic studies are required to establish correlation between improved dissolution and oral bioavailability. Scale-up studies, packaging optimization and long-term stability testing should also be performed to confirm industrial feasibility.

ACKNOWLEDGEMENT

The author acknowledges the support of the Department of Pharmaceutics and the laboratory facilities used for the formulation and evaluation work.

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