Int J App Pharm, Vol 16, Issue 5, 2024, 332-338Original Article
DRUG EXCIPIENT ADSORPTION TECHNIQUE FOR THE PREPARATION OF LOW-DOSE TABLETING
NIKHITHA K. SHANMUKHAN, RAMYA G., ARUN RADHAKRISHNAN*
Department of Pharmaceutics, JKKN College of Pharmacy, Namakkal-638183, Tamil Nadu, India
*Corresponding author: Arun Radhakrishnan; *Email: arunpharma93@gmail.com
Received: 29 Mar 2024, Revised and Accepted: 13 Jun 2024
ABSTRACT
Objective: This study aimed to improve drug mixability and drug uniformity in personalized medicine low-dose tablet by developing a stable, easily mixable, drug-adsorbed filler.
Methods: The research involved adsorbing drug onto filler by using three solvents and drug-to-excipient ratios of 1:50 and 1:75. The drug adsorbed fillers, were analyzed for drug content uniformity and flow properties, which are crucial for accurate dosing and manufacturing of low dose tablet.
Results: Formulations T1, T2 and T3 showed similar flow properties, including bulk and tapped densities, Carr's indices, and Hausner ratios. T1 had better flowability with a lower angle of repose (23.97 degrees) compared to T2 (35.42 degrees), T3 (49 degrees), and T4 (39 degrees) and it also had higher drug uniformity (99.89%, 99.54%, 97.12%, 96.83%). Tablet evaluations of TS1, TS2, TS3 and TS4 met standard criteria for weight variation, friability, and hardness criteria, with TS1 showing a quicker disintegration time (2:58 min), indicating faster dissolution and potentially better bioavailability. Dissolution tests showed both exceeded 85% drug release within 30 min, with TS1 achieving a higher release (99.98), suggesting more efficient drug release.
Conclusion: The drug-adsorbed filler premix technique effectively ensures drug content uniformity and improves low-dose drug mixing, contributing to the development of safe, efficient low-dose pharmaceuticals.
Keywords: Low-dose tableting, Cetirizine, Drug adsorbed fillers, Content uniformity, FTIR
© 2024 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/)
DOI: https://dx.doi.org/10.22159/ijap.2024v16i5.50991 Journal homepage: https://innovareacademics.in/journals/index.php/ijap
INTRODUCTION
Tablets, a widely utilized dosage form, offer advantages such as convenience, ease of administration, and precise dosing [1]. Low-dose tablets contain less potent active ingredients than their standard counterparts. They are designed to deliver gentler or more precise doses while minimizing the risk of adverse effects. Pharmaceutical manufacturing encounters significant challenges in maintaining precise content uniformity when drugs must be dispensed in very small doses, particularly when these medications possess a narrow therapeutic window. The manufacturing challenges in low dose drugs are primarily due to the small quantities of the active drug involved, which complicates achieving uniform mixing within the excipients [2]. Inaccurate doses in each tablet can result from improper distribution of the drug in the powder blend. This presents a significant challenge in precise drug delivery, especially in personalized medicine. In such cases Low dose mixing techniques are especially significant for potent drugs, where precise dosing is critical to achieve the desired therapeutic effects while minimizing the risk of overdose or serious side effects.
Both excipient and active ingredient characteristics and mixing processes influence the uniform drug distribution in the powder blend. Excipient characteristics significantly influence the blending process and final product quality, with poor flowing and cohesive drug substances posing difficulties in achieving homogeneity [3]. Various strategies, including selecting excipients, manufacturing processes, and equipment, have been employed to address these challenges and enhance the blending process and content uniformity of low-dose solid dosage forms. Some strategies include dissolving or dispersing the drug in a liquid vehicle and subsequently spraying the resulting solution onto a powder bed. Another approach involves blending micronized drugs with excipients and then granulating the blends with a granulating liquid. Alternatively, the binder solution can be sprayed onto an inert carrier matrix, followed by the spraying of microdose drug particles. Another method entails blending micronized drugs with suitable carrier excipients to create an interactive mixture where the micronized drug particles are adsorbed onto the carrier particles. Additionally, a dry granulation approach can be utilized. Each method offers distinct advantages depending on the specific requirements of the formulation and the desired properties of the final product [4, 5]. These technological advancements have significantly improved the manufacturing and quality of low-dose drug products by ensuring content uniformity during the mixing and formulation processes.
This study focused on preparing a filler-adsorbed premix containing a low-dose drug. It aimed to achieve uniform drug content in powder blends and ensure precise dosage in each tablet. This premix addresses the industrial challenges associated with mixing low doses.
MATERIALS AND METHODS
Cetirizine, Microcrystalline Cellulose (MCC), Polyvinylpyrrolidone (PVP), Sodium Starch Glycolate (SSG), Talc, Lactose, and Potassium Bromate were purchased from SD Fine Chemical Ltd., Mumbai, India. Ethanol was purchased from E. I. D-Parry Limited, India.
Preformulation studies
Preformulation studies are early-stage investigations in drug development that focus on understanding the physical and chemical properties of a drug candidate before formulating it into a final dosage form. These studies help select the right formulation techniques and ingredients to make a stable and effective medication. Top of FormPreformulation studies for cetirizine involves examining its melting point, λmax, solubility, and compatibility with other substances as part of the initial evaluation of the drug molecule [6].
Melting point
The determination of the melting point of cetirizine involves using the capillary tube method. In this approach, a capillary tube sealed at one end is filled with cetirizine. The filled capillary tube is then placed in a melting point apparatus. The temperature at which the cetirizine powder melts is observed and recorded [7].
Determination of λmax
A solution of cetirizine with a concentration of 10µg/ml in ethanol is prepared. The solution is analyzed using a Labindia UV/Vis double beam spectrophotometer, which scans the wavelength range of 200-400 nm [8].
Calibration curve of cetirizine
To prepare the standard calibration curve of cetirizine, 100 mg of the compound was accurately measured and transferred to a 100 ml volumetric flask. The powder was dissolved in 0.1N HCl, and the volume was made up to obtain a stock solution with a concentration of 1000µg/ml. Next, 10 ml of this stock solution was taken and diluted with 100 ml of 0.1N HCl, resulting in a solution with a concentration of 100µg/ml. Simultaneously, aliquots of appropriate volumes were taken in separate volumetric flasks. These solutions were made up to 10 ml using 0.1N HCl, generating six different concentrations (2, 4, 6, 8, 10 µg/ml). The UV absorbance readings at a wavelength of 230 nm were then recorded using a Labindia UV/Visible spectrophotometer.
Solubility studies
The solubility of cetirizine is determined using two solvents: water and dichloromethane ether, as well as alcohol (95%) and acetone. Separate beakers are used for each solvent, and an excess amount of cetirizine is added to each beaker. The mixtures are shaken periodically over 24 h using an orbitory shaker (NEOLAB). Afterward, the solutions were filtered using Whatman's filter paper (Grade No. 41). The filtered solutions were then analyzed using a spectrophotometer at 230 nm [10].
Compatibility study using fourier transform infrared spectroscopy (FTIR)
A small amount of cetirizine was mixed with Potassium Bromide (KBr) powder in a specified ratio. The mixture was then compressed under high pressure to form a pellet. Multiple pellets were prepared to ensure reproducibility. The prepared FTIR pellets were placed in the sample holder of the FTIR instrument. The instrument was operated to scan the samples in the mid-infrared region, typically between 4000 and 400 cm-1. The scan duration and number of accumulations were optimized to obtain reliable and representative spectra. A baseline spectrum, which represents the spectral characteristics of the KBr used in pellet preparation, was acquired without any sample. This baseline spectrum was subtracted from the sample spectra to remove any contribution from the KBr background. The obtained spectra were analyzed using suitable software. The spectra were examined for characteristic peaks, peak intensities, and any changes or shifts in peak positions. Spectral interpretation involves comparing the sample and reference spectra of the drug substance and excipients to identify potential interactions or chemical changes [11].
Table 1: Preparation of drug adsorbed diluents
| S. No. | Excipient and drug | T1 | T2 | T3 | T4 | T5 | T6 |
| 1 | Cetirizine | 0.5 mg | 0.5 mg | 0.5 mg | 0.5 mg | 0.5 mg | 0.5 mg |
| 2 | Lactose | 49.5 mg | 49.5 mg | 74.5 mg | 74.5 mg | 74.5 mg | 74.5 mg |
| 3 | Water | 30 ml | - | 30 ml | - | - | - |
| 4 | Ethanol | - | 30 ml | - | 30 ml | - | - |
| 5 | Acetone | - | - | - | - | 30 ml | 30 ml |
The procedure involved dissolving cetirizine in the solvent and subsequently adding the solvent-drug mixture to the lactose diluent. Thorough mixing ensured the uniform distribution of the drug within the diluent for each formulation. The variations in solvent and lactose concentration allowed for studying the effects on drug adsorption and formulation properties. In preparing T1 and T2 formulations, cetirizine (0.5 mg) was individually dissolved in either water or ethanol as the solvent. Subsequently, the solvent-cetirizine mixture was added to the lactose diluent (49.5 mg) and thoroughly mixed to ensure the uniform distribution of the drug within the diluent. For T1, 30 ml of water was used, while for T2, 30 ml of ethanol was employed as the solvent.
Similarly, in the preparation of T3 and T4 formulations, cetirizine (0.5 mg) was dissolved in the respective solvent, i. e., water or ethanol. The resulting solvent-cetirizine mixture was then added to a higher concentration of lactose diluent (74.5 mg) and mixed thoroughly to achieve a uniform distribution of the drug within the diluent. The T3 formulation utilized 30 ml of water as the solvent, while T4 employed 30 ml of ethanol, and T5 utilized 30 ml of acetone as the solvent [12].
Evaluation test for the prepared powders
Bulk and tapped density
The evaluation test for the prepared powders includes the determination of bulk and tapped density. For this test, a precisely weighed quantity of the powder (10g) is transferred into a 100 ml measuring cylinder, and the initial volume is marked as V1, representing the bulk volume. The cylinder is then tapped precisely 100 times, and the volume is marked as the tapped volume (bulk density apparatus). The bulk density is calculated using the formula: weight divided by V1. Similarly, the tapped density is determined by dividing the weight of the powder by the tapped volume. These formulas provide quantitative measurements of the powders' density characteristics, aiding in assessing their physical properties [13].
Carr’s index
Using the obtained values for bulk density (ρb) and tapped density (ρt), the Carr's index is calculated using the formula [14]:
Hausner’s ratio
Using the obtained values for bulk density (ρb) and tapped density (ρt), the Hausner ratio is calculated by dividing the tapped density by the bulk density [15].
Angle of repose
The angle of repose was determined by conducting tests using a clean, dry funnel positioned 1.5 cm above the ground. The sample was carefully dropped into the funnel, and the resulting spread of the sample's height and radius was observed. The angle of repose was calculated using the formula. The angle of repose was quantified by measuring the height (h) and radius (r) of the sample spread. This method allowed for the assessment of the flowability and cohesiveness of the formulated powder, providing insights into its potential for manufacturing low-dose tablets [16].
Here,
h = heap’s average height
r = heap’s average radius.
The angle of repose was quantified by measuring the height (h) and radius (r) of the sample spread. This method allowed for the assessment of the flowability and cohesiveness of the formulated powder, providing insights into its potential for manufacturing low-dose.
Drug distribution/drug content uniformity
Take representative samples of the prepared drug-adsorbed diluents, ensuring they are properly mixed and free-flowing. Weigh around 10 gs, accurately using a balance. Transfer the weighed sample to a suitable container. Add 30 ml of ethanol to dissolve the drug completely. Stir or shake the container to facilitate the dissolution of cetirizine in ethanol. Set up the UV-Visible spectrophotometer (Labindia). Measure the absorbance of the extracted solution containing cetirizine using the spectrophotometer at the specific wavelength of 247 nm. Repeat the analysis in triplicate for each sample to ensure accuracy and precision. Determine the average absorbance of the triplicate measurements for each sample. Use the calibration curve to correlate the average absorbance to the corresponding cetirizine concentration. Calculate the percentage of drug content in the prepared drug adsorbed diluents by dividing the calculated cetirizine concentration by the weight of the original sample and multiplying by 100 [17].
Table 2: Direct compression by using drug adsorbed diluents
| Batch/ingredients | TS1 | TS2 | TS3 | TS4 |
| Drug adsorbed diluents powder | 50 mg | 50 mg | 75 mg | 75 mg |
| MCC | 87.5 | 87.5 | 62.5 | 62.5 |
| PVP | 10 | 10 | 10 | 10 |
| SSG | 2 | 2 | 2 | 2 |
| Talc | 0.5 | 0.5 | 0.5 | 0.5 |
| Total weight | 150 mg | 150 mg | 150 mg | 150 mg |
Preparation of tablets
For the preparation of tablets using the direct compression method, the following procedure was followed for each TS1, TS2, TS3, and TS4. TS1 (Drug adsorbed diluents mixture 1): First, 50 mg of the drug-adsorbed diluents powder was accurately weighed and transferred into a suitable container. Then, 10 mg of PVP was added to the container, and thorough mixing was performed to ensure uniform distribution. Subsequently, 87.5 mg of MCC was added to the container, and mixing was continued until the PVP and MCC were well blended. Next, 2 mg of SSG was added to the mixture, followed by additional mixing to achieve homogeneity. Finally, 0.5 mg of Talc was added, and all the ingredients were mixed thoroughly. The same procedure was repeated for TS2, where 50 mg of drug adsorbed diluent powder (mixture 2) was used instead. The ingredient addition and mixing steps were performed in the same order as described for TS1. For TS3, 75 mg of the drug-adsorbed diluent powder (mixture 3) was accurately weighed and mixed following the identical procedure used for TS1, ensuring proper distribution of the ingredients. Similarly, for TS4, 75 mg of drug adsorbed diluent powder (mixture 4) was utilized, and the procedure was repeated as for TS3, adhering to the prescribed order of ingredient addition and mixing. After each mixture's mixing process, the resulting blends were ready for tablet compression using a tablet compression machine (Proton Minipress), considering the desired tablet specifications such as size, hardness, and disintegration time [18].
Evaluation of tablets
Thickness
A digital vernier caliper was utilized to determine the tablets' thickness. The measurement involved the use of five tablets to obtain an average value and ensure accuracy. The caliper was carefully positioned perpendicular to the tablet surface, and the jaws were gently closed to capture the tablet's thickness. The process was repeated for each tablet, and the recorded values were averaged to determine the overall thickness of the tablets [19].
Weight variation test
A weight variation test was conducted using a wensar electronic balance to assess weight variation. For each batch, twenty tablets were randomly chosen and individually weighed according to the official method specified for the test [20].
Hardness
Hardness is a crucial parameter that reflects a tablet's ability to withstand mechanical shocks during handling. The Monsanto hardness tester, capable of measuring hardness in kg/cm², was employed to determine the tablet hardness. Three tablets were randomly selected to obtain accurate results, and their hardness was measured using the Monsanto hardness tester. This step ensured a representative assessment of the tablet's mechanical strength and resistance to breakage [21].
Friability test
The Roche friability test is utilized to determine the friability of tablets, which is expressed as a percentage (%). Ten tablets are weighed (Wо) and placed into the friability tester, which runs for a hundred revolutions or operates at 25rpm for 4 min. After the process, the tablets are reweighed (W). Tablets with a friability exceeding 1% are deemed acceptable. This test evaluates the tablet's resistance to abrasion and ensures its durability during handling and transportation [22].
Disintegration test
The disintegration test was conducted following the Indian Pharmacopeia (IP) specifications. The instrument utilized for this test was the USP-Electro lab USP-ED-2AL disintegration tester. Six tablets were placed in the apparatus and filled with distilled water at a temperature of 37±0.2 °C. The tablets were deemed completely disintegrated when all particles had passed through the wire mesh. The time taken for disintegration was recorded, and the mean of two determinations was calculated. This method ensured compliance with the disintegration requirements specified by the IP and allowed for the assessment of the tablets' disintegration characteristics [23].
In vitro dissolution studies
The release rate of cetirizine from the tablets was determined using the paddle method of The United States Pharmacopoeia (USP) dissolution testing apparatus II. The dissolution test was conducted using 900 ml of 0.1N HCl at a temperature of 37±0.5ºC and a paddle rotation speed of 50 rpm. At specific time intervals, a 10 ml sample of the solution was withdrawn from the dissolution apparatus, and an equal volume of fresh dissolution medium was replaced. The withdrawn samples were suitably diluted with 0.1N HCl. The concentration of the samples was measured using a Labindia UV-Visible double beam spectrophotometer 1800 at a wavelength of 230 nm. Cumulative % of drug release was calculated using an equation derived from a standard curve. This approach enabled the evaluation of the release profile and dissolution characteristics of cetirizine from the tablets [24].
RESULTS AND DISCUSSION
Preformulation studies
Melting point
The melting point of the drug under investigation was determined using the capillary tube method and a melting point apparatus. The obtained result for the melting point was found to be 169 degrees Celsius. The melting point of a substance serves as a crucial indicator of its identity and purity. This result signifies that the compound possesses a well-defined and characteristic melting point consistent with the known literature value [25].
Determination of λmax
The determination of λmax for the cetirizine solution (10µg/ml) in acetone using the Shimadzu 1800 UV/Vis double beam spectrophotometer revealed a λmax value of 230 nm. The λmax indicates the wavelength at which the highest absorption of light occurs, allowing for accurate analysis and quantification of cetirizine in future studies [26].
Fig. 1: λmax of cetirizine
Calibration curve of cetirizine
The calibration curve for cetirizine was generated using absorbance data at 230 nm in 0.1 M HCl. Concentrations ranging from 0 to 10μg/ml were measured, and a linear regression analysis yielded an R² value of 0.9972. This high correlation coefficient demonstrates a strong relationship between concentration and absorbance, enabling accurate quantification of cetirizine in future analyses. The calibration curve serves as a reliable tool for determining cetirizine concentrations [27].
Table 3: Calibration curve of cetirizine
Concentration (μg/ml) |
Absorbance in 0.1N HCl |
0 |
0 |
2 |
0.17 |
4 |
0.29 |
6 |
0.41 |
8 |
0.57 |
10 |
0.69 |
Solubility studies
The solubility of cetirizine was investigated in water, ethanol (95%), acetone, dichloromethane, and ether. Cetirizine was found to be freely soluble in ethanol (95%) and acetone, sparingly soluble in water, and very slightly soluble in dichloromethane and ether. These solubility characteristics provide vital information for drug formulation and delivery, ensuring appropriate solvents are chosen to achieve desired dissolution rates [28].
Compatibility study using FTIR
A drug-excipient compatibility study was carried out using the FTIR method to evaluate the compatibility of the excipients (PVP, MCC, SSG, Talc) with the drug (cetirizine) in the formulation. The results of the analysis indicated that all the ingredients demonstrated compatibility with the drug [29].
Fig. 2: Calibration curve of cetirizine
Fig. 3: FTIR spectra of drug and excipients
Table 4: FTIR interpretation
| S. No. | Functional groups |
Peak values (cm-1) for cetirizine | Peak values (cm-1) for MCC succinate |
Peak values (cm-1) For PVP |
Peak values (cm-1) for talc | Peak values (cm-1) for SSG | Peak values (cm-1) lactose |
| 1 | C=C Stretching | 1614 | 1622 | ||||
| 2 | C-H Stretching alkane | 2715 | 2763 | 2925 | |||
| 3 | O-H bending | 1441 | 1429 | 1427 | 1321 | ||
| 4 | C-O Stretching alkyl aryl Ether | 1258 | 1286 | 1260 | |||
| 5 | C-H bending aromatic Compound | 1654 | 1668 | ||||
| 6 | CH2-CH2,-CH3 | 2900 | 2902 | ||||
| 7 | O-H Stretching strong broad | 3424 | 3526 | 3425 | 3772 | 3384 | |
| 8 | C=O stretching | 1740 | |||||
| 8 | CH2bending | 1018 | 1039 | 900 | |||
| 9 | C-O Stretching | 1068 |
Preparation of drug-adsorbed diluents
Drug-absorbed diluents were prepared using lactose as the diluent material and ethanol and water as the solvents. Various ratios of diluents and solvents were tested to assess their influence on drug absorption properties. The objective was to identify the optimal ratio that would enhance drug absorption. This study aims to optimize the formulation by determining the most effective diluent-solvent combination for improved drug uniformity and ease of mixing [30].
Evaluation of drug-adsorbed diluents
Flow properties
These parameters provide insights into the flow characteristics and suitability of the diluents for pharmaceutical manufacturing processes. Among the batches, T1 and T2 displayed more favorable flow properties. Batch T1 exhibited a bulk density of 0.423 g/cm³, a tapped density of 0.396 g/cm³, a Carr's index of 6.82%, a Hausner ratio of 0.94, and an angle of repose of 23.97 degrees. Similarly, T2 showed a bulk density of 0.479 g/cm³, a tapped density of 0.559 g/cm³, a Carr's index of 14.31%, a Hausner ratio of 1.17, and an angle of repose of 35.42 degrees. In contrast, batches T3 and T4 demonstrated relatively poorer flow properties. T3 had a bulk density of 0.346 g/cm³, a tapped density of 0.476 g/cm³, a Carr's index of 27.31%, a Hausner ratio of 1.38, and an angle of repose of 49 degrees. T4 exhibited a bulk density of 0.464 g/cm³, a tapped density of 0.604 g/cm³, a Carr's index of 23.18%, a Hausner ratio of 1.30, and an angle of repose of 39 degrees. Based on these findings, it can be concluded that T1 and T2 are more suitable for pharmaceutical applications [31].
Table 5: Bulk density, tapped density, Carr’s index, Hausner’s ratio, Angle of repose
| Batch | Bulk density | Tapped density | Carr’s index (%) | Hausner’s ratio | Angle of repose |
| T1 | 0.423±0.02 | 0.396±0.011 | 6.82±0.32 | 0.94±0.012 | 23.97±0.013 |
| T2 | 0.479±0.01 | 0.559±0.03 | 14.31±0.04 | 1.17±0.019 | 35.42±0.021 |
| T3 | 0.346±0.13 | 0.476±0.06 | 27.31±0.12 | 1.38±0.010 | 49±0.071 |
| T4 | 0.464±0.09 | 0.604±0.15 | 23.18±0.03 | 1.30±0.021 | 39±0.031 |
Results are represented as mean±SD (n=3)
Drug content uniformity
From the obtained results, trials T1 and T2 demonstrate drug content uniformity values of 99.89% and 99.54%, respectively, which fall within the acceptable range. The results indicate that the drug is uniformly distributed in the samples, ensuring consistent dosing. However, trials T3 and T4 exhibit slightly lower drug content uniformity values of 97.12% and 96.83%, respectively. The variability in drug content may be due to the variability in drug distribution in various trials. It is important to note that deviations from the specified range may impact the efficacy and safety of the medication. The variability may be attributed to changes in the ratio of diluent and cetirizine used in the formulation [32].
Table 6: Drug content uniformity
| S. No. | Trials | Drug content uniformity |
| 1 | T1 | 99.89±0.076 |
| 2 | T2 | 99.54±0.551 |
| 3 | T3 | 97.12±0.23 |
| 4 | T4 | 96.83±0.21 |
Drug content uniformity values are represented as mean±SD, number of experiments (n=3)
Preparation of tablets
Direct compression by using drug-adsorbed diluents
The drug-adsorbed diluent powder was used for low-dose mixing, while the other excipients were chosen for their specific functions. MCC acted as a filler and binder, providing cohesion to the tablet matrix. PVP served as a binder, enhancing the tablet's mechanical strength. SSG was included as a super disintegrant to promote rapid disintegration of the tablet upon administration. Talc was used as a glidant to improve the flow properties of the formulation. The direct compression method involved thoroughly blending the ingredients, followed by compression into tablets using a Proton Minipress [33].
The analysis of the prepared tablets revealed consistent weight variation within the acceptable limit of 2%. The friability values ranged from 0.19% to 0.29%, indicating that the tablets exhibited good mechanical strength. The hardness values ranged from 5 kg/cm² to 6 kg/cm², meeting the standard range. The disintegration time was within the specified limit of 15 min, indicating effective dissolution [34].
Table 7: Tablet evaluation
| Batch/Evaluation | Weight variation (%) | Friability (%) | Hardness (kg/cm²) | Disintegration time |
| T1 | 2±0.023 | 0.29±0.65 | 5±0.011 | 2 min 58S |
| T2 | 2±0.13 | 0.22±0.42 | 6±0.021 | 3 min 10S |
| T3 | 3±0.071 | 0.20±0.012 | 6±0.070 | 3 min 15S |
| T4 | 2±0.12 | 0.19±0.82 | 6±0.032 | 4 min |
Results are represented as mean±SD, number of experiments (n=3)
Table 8: Percentage cumulative drug release
| Time | TS1 | TS2 | TS3 | TS4 |
| 0 | 0 | 0 | 0 | 0 |
| 5 | 32.5±0.02 | 26.67±0.06 | 20.18±0.03 | 21.87±0.51 |
| 10 | 76.02±0.45 | 65.32±0.42 | 62.32±0.42 | 60.24±0.07 |
| 15 | 96.12±0.04 | 91.49±0.65 | 90.87±0.12 | 90.72±0.26 |
| 30 | 99.98±0.01 | 99.91±0.07 | 98.11±0.11 | 97.64±0.031 |
The % cumulative drug release values are represented as mean±SD, n=3
Fig. 4: % cumulative drug release from TS1, TS2, TS3 and TS4. Error bars indicate SD values, n=3
According to the IP standard, the desired drug release limit is 85% within 30 min. The data shows that all formulations exceeded this standard, with TS1 and TS2 achieving drug releases of 99.98% and 99.91%, respectively, at the 30 min mark. Formulations TS3 and TS4 also exhibited high drug releases of 98.11% and 97.64%, respectively, within the given time frame. Based on these results, all the formulations demonstrated excellent drug release profiles, surpassing the IP requirement. However, formulations TS1 and TS2 exhibited the highest drug releases, indicating their potential for efficient drug delivery [35-38].
CONCLUSION
Compared to T2, T1 showcases comparable flow properties, as both formulations exhibit acceptable bulk densities, tapped densities, Carr's indices, and Hausner ratios. However, T1 demonstrates a lower angle of repose (23.97 degrees) than T2 (35.42 degrees), indicating better flowability and ease of processing. In terms of drug content uniformity, T1 (99.89%) outperforms T2 (99.54%), ensuring more consistent dosing and uniform distribution of the drug within the tablets. Regarding tablet evaluation, T1 and T2 display similar weight variation, friability, and hardness values, meeting acceptable standards. However, T1 exhibits a slightly shorter disintegration time (4 min and 58 seconds) than T2 (5 min and 10 seconds), suggesting faster dissolution and potentially enhanced bioavailability. In the dissolution studies, T1 and T2 surpass the IP standard requirement of 85% drug release within 30 min. However, T1 achieves a higher drug release percentage of 99.91% at the 30-minute mark, while T2 achieves 98.79%. This indicates that T1 offers more efficient drug release, ensuring optimal therapeutic effects. Considering these comparisons, T1 consistently demonstrates superior flow properties, drug content uniformity, disintegration time, and drug release. The results indicate that T1 offers more efficient drug release, ensuring optimal therapeutic effects. Considering these comparisons, T1 consistently demonstrates superior attributes in terms of flow properties, drug content uniformity, disintegration time, and drug release.
FUNDING
Nil
AUTHORS CONTRIBUTIONS
Dr. Arun Radhakrishnan: Ideation, strategizing and planning, Nikhitha K S: Execution and formulation, Ramya G: Evaluation and drafting.
CONFLICT OF INTERESTS
Declared none
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