Development and Evaluation of Sustained Release Aspirin Tablets Using Synthetic and Natural Polymer

Mr. Imran Khan, Mr. Md Shaikh Kamran, Mr. Pathan Rahemat Khan, Mr. Tare Dipak,

Dr. R.D. Ingole, Mr. Kale Shyam Shirishkumar*

Department of Pharmacy, DJPS College of Pharmacy, Pathri, Parbhani, Maharashtra, India

Correspondence: djpssk@gmail.com
DOI: https://doi.org/10.71431/IJRPAS.2026.5604

 INTRODUCTION

Oral sustained-release drug delivery systems have gained significant importance in modern pharmaceutical research because they improve therapeutic efficacy and reduce the limitations associated with conventional dosage forms.(1) Conventional tablets often produce fluctuations in plasma drug concentration, resulting in repeated dosing, variable therapeutic effects, and an increased risk of side effects.(2)  Sustained-release matrix tablets are designed to overcome these problems by maintaining drug release at a controlled rate over an extended period, thereby improving patient compliance and therapeutic outcomes.(3)

Aspirin is widely used as an analgesic, antipyretic, anti-inflammatory, and antiplatelet drug. However, its conventional dosage forms may require frequent administration and may produce gastrointestinal irritation due to rapid drug release.(4) Therefore, the development of a sustained-release formulation can help maintain effective plasma concentrations for a prolonged period and minimize adverse effects associated with repeated dosing. Matrix tablet systems are among the most commonly employed approaches for sustained drug delivery because of their simple manufacturing process, cost effectiveness, and ability to control drug release through polymeric networks.(5) Previous studies have reported the use of synthetic polymers such as Hydroxypropyl Methylcellulose (HPMC) and natural polymers including gum acacia in sustained-release formulations due to their swelling and release-retarding properties. However, limited studies have explored the combined use of synthetic and natural polymers in aspirin sustained-release tablets. The objective of the present study is to formulate and evaluate sustained-release matrix tablets of aspirin using a combination of HPMC E15 and gum acacia by direct compression to achieve prolonged and controlled drug release.

Sustained Release Drug Delivery System:

Sustained-release drug delivery systems are pharmaceutical formulations designed to release a drug at a predetermined rate for an extended period of time, maintaining therapeutic drug concentrations in the body while minimizing fluctuations associated with conventional dosage forms.(6)  These systems are developed to improve drug efficacy and reduce the frequency of administration by prolonging the duration of action. Sustained-release formulations are intended to modify the release characteristics of a drug by incorporating suitable polymers and excipients that regulate drug diffusion, dissolution, or erosion mechanisms.(7) Unlike immediate-release dosage forms, where the drug is rapidly released after administration, sustained-release systems provide gradual and controlled delivery of the active ingredient.(8) The design of sustained-release systems depends on several factors including physicochemical properties of the drug, biological half-life, absorption characteristics, and pharmacokinetic behavior.(9) Such formulations help maintain drug concentration within the therapeutic window for a longer duration and reduce the occurrence of peak and trough plasma concentration levels.(10) Sustained-release systems are widely used in the treatment of chronic conditions requiring prolonged therapy, such as cardiovascular disorders, arthritis, and pain management.(11) The incorporation of natural and synthetic polymers has further improved the effectiveness of these systems by providing better control over drug release behavior and enhancing patient convenience.(12)

MATERIALS AND METHODS

Aspirin was used as the active pharmaceutical ingredient (API) for the preparation of sustained-release matrix tablets. Hydroxypropyl methylcellulose E15 (HPMC E15) and gum acacia were used as synthetic and natural polymers, respectively, for controlling drug release. Microcrystalline cellulose and starch were used as diluents, while talc and magnesium stearate were used as glidant and lubricant, respectively. All materials used in the study were of analytical grade and procured from Dipa Chemical Industries.

Table 1: Materials used in the study

Equipment:

The instruments used during the study included a UV–Visible Spectrophotometer (SHIMADZU-1900i, Japan), electronic balance (Essae AJ-220L), ultrasonicator (Citizen), melting point apparatus (Macro Scientific Works), Monsanto hardness tester, Roche friabilator, dissolution apparatus USP Type II (Paddle), Vernier caliper, and disintegration test apparatus.

Pre-formulation Studies:

Pre-formulation studies were performed to determine physicochemical properties of aspirin that could influence formulation development and performance. Parameters evaluated included organoleptic characteristics, solubility, melting point, UV spectrophotometric analysis, and micromeritic properties.

Identification and Characterization of Aspirin:

The organoleptic properties such as color, odor, and appearance of aspirin were observed visually. Solubility studies were performed using water, ethanol, and phosphate buffer. The solubility behavior was recorded as soluble, slightly soluble, or insoluble.

The melting point of aspirin was determined using the capillary tube method with a melting point apparatus. The temperature range at which the sample started melting and completely melted was recorded.

Solubility Study:

The solubility of aspirin was determined by the shake-flask method. An excess amount of aspirin was added separately to distilled water, ethanol, methanol, and phosphate buffer pH 6.8. The mixtures were shaken periodically at room temperature until equilibrium was attained. The solutions were then filtered, and the solubility of aspirin in different solvents was observed visually and recorded.(14)

UV Spectrophotometric Analysis: The λmax of aspirin was determined using a double-beam UV–Visible spectrophotometer by scanning the sample solution of 10 µg/mL over a wavelength range of 200–400 nm.

Preparation of Phosphate buffer (pH 6.8): It was prepared by dissolving 6.8 g of potassium dihydrogen phosphate (KH₂PO₄) in approximately 250 mL of distilled water. To this solution, 77 mL of 0.2 N sodium hydroxide solution was added, and the volume was adjusted to 1000 mL with distilled water. The resulting buffer solution was thoroughly mixed, and the pH was verified with a calibrated pH meter and adjusted to 6.8 ± 0.05 as needed. The prepared phosphate buffer (pH 6.8) was used as the dissolution medium for the in vitro drug release studies.(15)

Standard calibration curve:

Stock Solution 1: Accurately weighed 100 mg of Aspirin was transferred into a 1000 mL volumetric flask and dissolved in phosphate buffer pH 6.8. The volume was made up to 1000 mL with the same buffer to obtain a stock solution containing 100 µg/mL of Aspirin.

Stock Solution 2: From Stock Solution 1, suitable aliquots were diluted with phosphate buffer pH 6.8 to obtain a working standard solution containing 100 µg/mL of Aspirin.

Preparation of Calibration Standards: Aliquots of 1, 2, 3, 4, and 5 mL were withdrawn from Stock Solution 2 (100 µg/mL) and transferred into separate 50 mL volumetric flasks. The volume was adjusted to 50 mL with phosphate buffer pH 6.8 to obtain concentrations of 2, 4, 6, 8, and  , respectively. The absorbance of these solutions was measured at λmax using phosphate buffer pH 6.8 as blank. A calibration curve was plotted between concentration and absorbance.

Evaluation of Powder Blend: The powder blend was evaluated for micromeritics properties including angle of repose, bulk density, tapped density, Carr’s index, and Hausner ratio.(16) (17)

Bulk density: It was determined by pouring a known quantity of powder into a graduated measuring cylinder and recording the bulk volume.

Bulk density was calculated using:         ρb = M/Vb

Where:

M = Weight of powder
Vb = Bulk volume

Angle of repose: It was determined using the funnel method and calculated according to the following equation:                                                 Tan θ = h/r

Where:

θ = Angle of repose
h = Height of powder cone
r = Radius of cone base

Tapped density: It was determined by mechanically tapping the measuring cylinder containing the powder until a constant volume was obtained.

Tapped density was determined using:                ρt = M/Vt

Where:

M = Weight of powder blend
Vt = Tapped volume

Carr's compressibility index:

It was calculated using:    Carr's Index (%) = [(TBD − LBD)/TBD] ×100

                                     Where,

 TBD=Tapped density

 LBD=Loose bulk density

Hausner ratio:

It was determined using:

                                        Hausner Ratio = TBD/LBD

Formulation of Sustained Release Tablets:

Sustained-release matrix tablets of aspirin were prepared by direct compression technique. All ingredients were accurately weighed according to the formulation design and passed through sieve number 60. Aspirin, HPMC E15, gum acacia, microcrystalline cellulose, and starch were blended thoroughly. Talc and magnesium stearate were added and mixed for an additional 3–5 minutes.(18) (19)

The final blend was compressed using a rotary tablet compression machine by adjusting compression force appropriately to obtain tablets without capping or chipping defects.

Table 2: Formulation of Aspirin Sustained Release Tablets

Evaluation of Tablets

Prepared tablets were evaluated for hardness, thickness, friability, weight variation, disintegration time, and in-vitro dissolution.

Tablet hardness

Hardness Test:

Tablet hardness was determined using a Monsanto hardness tester. The tablet was placed between the jaws of the tester, and pressure was applied until it fractured. The force required to break the tablet was recorded as hardness and expressed in kg/cm².(20)

Thickness was determined using a Vernier caliper.

Friability Test:

The friability of the prepared tablets was evaluated using a Roche friabilator. A sample of tablets was accurately weighed and the initial weight (W₁) was recorded. The tablets were then placed in the friabilator and rotated at 25 rpm for 100 revolutions. After completion of the test, the tablets were dedusted and reweighed to obtain the final weight (W₂). The percentage friability was calculated from the difference between the initial and final weights. A friability value of less than 1% was considered acceptable, indicating adequate mechanical strength of the tablets.(21)

Friability was calculated using:

F = [(Winitial − Wfinal)/Winitial] ×100 .......... (6)

Where:

Winitial = Initial tablet weight
  Wfinal = Final tablet weight

Weight variation test:

Weight variation test was performed by individually weighing 20 tablets and comparing with the average weight.(20)

In-vitro Dissolution Study:

In-vitro drug release studies were performed using USP dissolution apparatus Type II (Paddle method). One tablet was placed in 900 mL phosphate buffer maintained at 37 ± 0.5°C and stirred at 50 rpm. Samples were withdrawn at predetermined intervals, filtered through a 0.45 μm membrane filter, and analyzed at 273 nm using UV spectrophotometry. The withdrawn volume was replaced with equal amounts of fresh dissolution medium.(22) (23)

RESULT AND DISCUSSION

Pre-formulation Studies:

Organoleptic Properties: The organoleptic characteristics of aspirin were evaluated to determine its physical appearance and general identity. Aspirin was observed as a white crystalline powder having a characteristic odor and slightly acidic taste, which agreed with standard reported characteristics and confirmed the identity of the drug.

Table 3. Organoleptic Properties of Aspirin

Melting Point Determination: The melting point of aspirin was determined using the capillary tube method and found to be 135.5°C

Solubility Determination: The solubility study revealed that aspirin was slightly soluble in distilled water and readily soluble in ethanol, methanol, and phosphate buffer pH 6.8. The good solubility of aspirin in phosphate buffer pH 6.8 supported its selection as the dissolution medium for in vitro drug release studies.

UV Spectrophotometric Analysis

UV spectrophotometric analysis confirmed the identity of aspirin by exhibiting characteristic absorption in the UV region.

λmax Determination

The λmax of aspirin in phosphate buffer pH 6.8 was found at 276 nm.

Fig 1. UV Spectrum of Aspirin Showing λmax at 276 nm

Calibration Curve

The calibration curve of aspirin was prepared at 276 nm and obeyed Beer–Lambert’s law over the selected concentration range.

Table 4. Solubility Study of Aspirin

Fig 2. Calibration curve of Aspirin

The linear relationship between concentration and absorbance indicated suitability of the analytical method for drug estimation.

Evaluation of flow Properties: Pre-compression parameters demonstrated acceptable flow properties and compressibility characteristics for all formulations.

Table 5. Pre-compression Parameters

Evaluation of Tablets:

Table 6. Post compression Parameters

In-vitro Dissolution Study

The in-vitro drug release study demonstrated sustained release behavior of aspirin over a period of 12 hours.

Table 13. Comparative In-vitro Drug Release Profile of F1–F3

Fig 3. % Cumulative Drug Release

CONCLUSION

The present study successfully developed sustained release matrix tablets of aspirin using Hydroxypropyl Methylcellulose E15 (HPMC E15) and Gum Acacia through the direct compression method. The prepared formulations exhibited satisfactory pre-compression and post-compression characteristics and complied with acceptable pharmacopoeial requirements, indicating good flow properties, mechanical strength, and tablet quality.

The formulation variables significantly influenced drug release behavior. The matrix-forming properties of HPMC E15 and Gum Acacia effectively controlled aspirin release by hydration and gel formation mechanisms. Among the prepared formulations, F3 demonstrated the most desirable sustained release characteristics with 99.4% cumulative drug release over 12 hours.

The findings of this study indicate that the combination of synthetic and natural polymers can be effectively utilized in developing sustained release aspirin tablets with prolonged drug release behavior. Such a formulation approach may improve therapeutic efficacy, reduce dosing frequency, and enhance patient compliance. Furthermore, this matrix system may provide a useful platform for the development of sustained release formulations of other drugs requiring prolonged therapeutic action.

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest

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