Formulation and Evaluation of Artemether Tablet by using Liquisolid Technique

Rakesh M. Wagh, Rajendra K. Surawase

Department of Pharmaceutics, Loknete Dr. J. D. Pawar College of Pharmacy,

Manur (Kalwan) 423501, Maharashtra, India.

*Corresponding Author E-mail: waghrakesh6484@gmail.com

ABSTRACT:

Artemether is a poorly water-soluble antimalarial drug, Its oral bioavailability is limited. The current study's objective was to improve medication release and dissolution by creating and evaluating Artemether immediate-release tablets utilizing the Liquisolid Technique. Direct compression was used to manufacture the tablets, and FTIR and UV spectroscopy were used to characterize them confirms drug integrity and compatibility. The precompression and postcompression properties of eight formulations (TF1–TF8), Drug content, thickness, hardness, friability, weight fluctuation, disintegration time, and in vitro dissolution profile were among the factors that were designed and evaluated. Formulation F8 had the best properties of all, showing better solubility and quick drug availability with a drug content of 99.86±0.02, a disintegration time of 5±0.03 min, and a percentage of drug release of 98.89±0.22 within 25 minutes. The study comes to the conclusion that the liquisolid compact technology is a viable strategy for improving artemether's rate of dissolution and immediate therapeutic impact.

KEYWORDS: Artemether, Antimalarial, Immediate-release, Solubility, Availability.

INTRODUCTION:

Medicines taken by mouth in solid form, they need to dissolve properly in the body to be absorbed into the blood. If a drug doesn’t dissolve well in water, it dissolves slowly and is absorbed poorly. This leads to low bioavailability, meaning the drug may not work as well. Two important things that affect how well a drug is absorbed are its solubility and permeability.^1,2

If a drug is not soluble, it can’t reach the needed level in the blood to be effective, many methods have been used to help poorly soluble drugs dissolve better. These include making the drug particles smaller (micronization or nanonization), using solid dispersions, or forming nanosuspensions. While helpful, these methods can be expensive or complicated.³ A newer and simpler approach is the liquisolid technique, developed by Spireas. A liquid medicine or a drug dissolved in a non-volatile solvent can be turned into a dry, free-flowing powder using this procedure. This powder can then be used to make tablets or capsules. Since the drug is already in a dissolved state, it dissolves more quickly in the body, leading to faster and better absorption.^4,5

The liquisolid method is especially useful for drugs in BCS Class II and IV, which have poor solubility. This technique is simple, cost-effective, and suitable for large-scale production.⁶ Artemether, an antimalarial drug, has short half-life and weak water solubility, which limits how well it works when taken by mouth. Using the liquisolid technique for Artemether can improve how fast and how much of the drug is absorbed, leading to better treatment results.⁷

MATERIAL:

Artemether was kindly provided by Micro Orgo-Chem, Vapi (Gujarat). Aerosil 200 and Polyethylene Glycol 400 were received in Modern Industries, Malegaon (Sinner). Sodium starch glycolate, Croscarmellose sodium, Crospovidone, and Magnesium Stearate were supplied by Research Lab Fine Chemical Industries, Mumbai. Microcrystalline cellulose and Mannitol were obtained from Balaji Drugs.

METHOD

Spectrometric Analysis:

To measure the analytical wavelength (λmax) of Artemether, 10mg of precisely weighed Artemether was dissolved in 70ml of methanol in a 100ml volumetric flask. Once the volume reached 100ml, methanol was added to create a stock solution with 100μg/ml. They took 2.5ml of this stock and diluted it with 10ml of methanol to get a 10μg/ml solution. When this solution was scanned between 200 and 400nm using a UV-visible spectrophotometer, the absorbance at 215nm was the highest. Solutions of varying concentrations (5–25μg/ml) were made from the stock for the calibration curve, and methanol was used as the solvent to measure the solutions' absorbance at 215nm.⁸

A 100ml volumetric flask was used to properly weigh 10mg of artemether and dissolve it in 20ml of methanol in order to measure the drug's maximum wavelength (λmax) in pH 6.8 phosphate buffer. After that, the standard solution was made using phosphate buffer, increasing the volume to 100 milliliters. A 10 μg/ml solution was obtained by further diluting 1ml with the same buffer to make 10ml. The λmax of this solution was determined to be 215nm after it was scanned with a UV-visible spectrophotometer between 200 and 400nm. A range of concentrations from 5 to 25μg/ml were generated for the calibration curve, and using UV spectroscopy with phosphate buffer as the solvent, their absorbance was measured at 215nm.⁸

Determination of Preformulation Parameters:

When studying the flow and packing properties of powders and granules, it's important to consider factors like tapped density, bulk density, Hausner's ratio, Carr's index, and angle of repose. Bulk and tapped densities measure how much mass is packed into a certain volume, both before and after tapping. The angle of repose gives us an idea of how the particles' friction affects how they pile up. Hausner's ratio helps us understand how easily the powder flows, while Carr's index tells us how compressible the particles are. For effective powder handling in sectors including materials research, food, and pharmaceuticals, these qualities are essential.^8,9

FTIR:

IR spectroscopy is a useful technique to study how drugs interact with polymers and other excipients during storage. In this case, it was used to examine how excipients interact with Artemether. In order to look for any chemical changes, the IR spectra of the drug by itself and a physical mixture of the drug and excipients were compared. An interaction between the compounds is indicated if the spectra differ. A FTIR spectrophotometer operating in the wavelength range of 4000-400 cm⁻¹ was used to evaluate samples that were kept in a stability chamber. Artemether and excipients were combined in a 1:1 ratio, and other drug-loaded powders were analyzed using the same technique.⁹

Differential Scanning Colorimetry (DSC):

Differential scanning calorimetry (DSC) of Artemether and its excipients was conducted using a Shimadzu DSC-60plus instrument to study their thermal properties. Samples of Artemether and the excipients, mixed in a 1:1 ratio, were heated in aluminum pans from 25°C to 300°C at a rate of 10°C per minute to observe their thermal behavior.^9,10

Saturation Solubility of API:

Artemether saturation solubility experiments aid in figuring out how much of the drug dissolves in different non-volatile solvents. At a specific temperature, excess Artemether is added to the non-volatile solvent and agitated until it dissolves completely. Using techniques like UV spectroscopy, the amount of dissolved Artemether is determined after the remaining undissolved medication has been isolated. This study contributes to our understanding of the drug's solubility, which is critical to both its efficacy and the body's ability to absorb it.

Tablet Preparation:

To create a medication solution, artemether was first dissolved in Polyethylene Glycol 400 (Non-volatile solvent). Using a mortar & pestle, Mannitol (Carrier) was introduced gradually while being continuously mixed. The coating substance Aerosil 200 was then added to the mixture. The necessary amounts of lubricant (Mg. stearate), binder (MCC), and disintegrants (SSG, croscarmellose sodium, and crospovidone) were then well combined. After the mixture was run through sieves 40 and 60, the granules were dried for an hour at 60°C in a tray dryer. Lastly, a tablet punch was used to compress the dried granules into tablets.^9,10

Composition of Artemether Tablet:

Table 1: Composition of Artemether Tablet:

Sr. No	Ingredients	TF1	TF2	TF3	TF4	TF5	TF6	TF7	TF8
1	Artemether	20	20	20	20	20	20	20	20
2	PEG-400	0.6	0.6	0.6	0.6	0.6	0.6	0.6	0.6
3	Mannitol	139	135	131	127	135	135	131	131
4	Aerosil 200	15	15	15	15	15	15	15	15
5	Sodium Starch Glycolate	4	4	8	8	4	8	8	4
6	Croscarmellose sodium	4	8	4	8	4	4	8	8
7	Crospovidone	4	4	8	8	8	4	4	8
8	MCC	10	10	10	10	10	10	10	10
9	Mg. Stearate	4	4	4	4	4	4	4	4
Tablet weight		200	200	200	200	200	200	200	200

Note: The above ingredients are all in mg, but PEG 400 is in ml.

In order to improve Artemether's solubility in liquisolid formulations, In the current study, the coating material (Aerosil 200), the liquid vehicle (PEG 400), and the carrier was mannitol. The proper ratios of coating and carrier components were determined using a mathematical model to offer optimal flowability and compressibility. This model mainly depends on two key factors: the compressible liquid retention potential (Ψ-value) and the flowable liquid retention potential (Φ-value).

R = Q /q

Where, R= Ratio of carrier: coating material, Q= Carrier material weight, q= Coating material weight

Liquisolid tablet formulations often use carrier: coating material ratios 5:1, 7.5:1, and 10:1, according to Jaydip et al. (2020). The Lf is the ratio of the amount of liquid medication (W) to the amount of carrier material (Q), according to the mathematical model.

LF= W/Q

Where, W= Liquid blend weight, Q= Carrier materials weight

To ensure proper flow and compaction, Lf must not exceed a certain limit, calculated using the formulas:

ΦLf = Φ + φ (1/R) → for flowability

ΨLf = Ψ + ψ (1/R) → for compressibility

The optimum Lf is the lower value between ΦLf and ΨLf. ^{10, 11}

Determination of Postformulation Parameters:

The result of tablets is assessed through several tests: thickness is measured using a Vernier Caliper in mm; hardness is determined using a hardness tester, with force gradually applied until the tablet breaks, and results are expressed in kg/cm²; weight variation is checked by weighing 20 randomly selected tablets; and friability is measured using a friabilator, This refers to calculating the percentage of tablet weight lost after the tablets are rotated.These tests ensure the tablets meet required standards for uniformity and durability.¹¹

Drug Content:

To determine the drug content, 20 tablets were ground into powder, and 100mg of the powder was mixed with 100ml of a 6.8 pH phosphate buffer solution. The mixture was stirred for 30 minutes, then filtered. The absorbance of the filtered solution was measured at 215 nm using a UV-visible spectrophotometer, after the solution was diluted with the same 6.8 pH phosphate buffer.¹²

In-vitro drug release studies:

The USP-II tablet dissolution testing instrument can be used to measure the release rate of Artemether from liquisolid compact (corresponding to 10mg of Artemether) at a rotation speed of 50rpm. At 37±0.5ºC, 900ml of 6.8 Phosphate Buffer solutions were used for the dissolving test. A 5ml aliquot sample was removed and replaced with new media every two minutes. Using a spectrophotometer set to 215nm, the quantity of Artemether in each pharmaceutical solution was determined.¹³

Table 3: Dissolution Parameters

Sr.No.	Parameters	Specifications
1	USP dissolution device	Type II [Paddle method]
2	Dissolution medium volume	900 ml
3	Rotation speed	50 rpm
4	Temperature	37º±0.5ºC
5	Medium of dissolution	Phosphate buffer pH 6.8
6	Sample withdraw at each time interval	5ml

RESULT AND DISCUSSION:

Spectrometric Analysis:

Using UV spectroscopy, Artemether's maximum absorption wavelength (λmax) was determined to be 215 nm, as shown in Fig. 1.

Fig.1: Analytical wavelength (λmax) of Artemether

A good linear relationship between concentration and absorbance is demonstrated by the standard calibration curve for Artemether, Its slope is y = 0.0238x+0.0134, and its coefficient of regression value is R2 = 0.999 (Fig. 2).

Table.4: Concentration and Absorbance value for Artemether in methanol

Sr. No	Concentration (μg/ml)	Absorbance at 215nm
1.	5	0.125
2.	10	0.260
3.	15	0.371
4.	20	0.488
5.	25	0.605

Fig.2: Calibration curve of Artemether in Methanol

· The UV spectrum of Artemether (10mg/ml) was scanned between 200 to 400nm. In 6.8 phosphate buffer. Artemether showed its maximum absorption wavelength at 215nm (Fig.3).

Fig.3: UV Spectrum of Artemether in 6.8 Phosphate Buffer

A calibration curve for Artemether was created in a 6.8 pH phosphate buffer. The curve showed a straight-line relationship within the concentration range of 5–25 μg/ml, with the equation y = 0.0206x + 0.0682 and a high regression value of R² = 0.9988. Figure 4 shows the Artemether calibration curve in this buffer.

Table.5: Concentration and Absorbance value for Artemether in 6.8 Phosphate Buffer

Sr. No	Concentration (μg/ml)	Absorbance at 215 nm
1.	5	0.172
2.	10	0.268
3.	15	0.386
4.	20	0.478
5.	25	0.582

Fig.4: Artemethers calibration curve in 6.8 Phosphate Buffer

Precompression evaluation of Liquisolid Tablet:

Table 5: Precompression evaluation of Liquisolid Tablet

Formulation	Bulk density (g/ml)	Tapped density(g/ml)	Carr’s index (%)	Hausner’s ratio	Angle of repose (θ)
TF1	0.44±0.08	0.49±0.02	10.20±0.10	1.11±0.33	33.12±1.13
TF2	0.42±0.03	0.47±0.06	10.63±0.09	1.11±0.41	31.66±1.28
TF3	0.45±0.11	0.50±0.04	10.00±0.15	1.11±0.63	29.85±1.43
TF4	0.40±0.06	0.45±0.02	11.11±0.08	1.12±0.58	27.10±1.21
TF5	0.43±0.02	0.48±0.01	10.41±0.03	1.11±0.29	32.94±1.30
TF6	0.45±0.12	0.50±0.08	10.00±0.20	1.11±0.38	31.12±1.24
TF7	0.41±0.04	0.46±0.02	10.86±0.06	1.12±0.54	28.90±1.48
TF8	0.42±0.11	0.47±0.04	10.63±0.15	1.11±0.21	29.20±1.33

The powder mixes of all eight liquisolid formulations showed tapped densities between 0.45 and 0.50g/ml and bulk densities between 0.40 and 0.45g/ml when pre-compression parameters were taken into consideration. There was a range of 27.10º to 33.12º for the angle of repose, 1.11 to 1.12 for the Hausner's ratio, and 10.00% to 11.11% for the Carr's index. These findings demonstrate the blends' superior flowability and compressibility as well as their compliance with approved pharmaceutical standards.

FTIR:

Fig. 5: Pure drug of Artemether

Fig. 6: Artemether+ Crospovidone

Fig. 7: Artemether + SSG

Fig. 8: Artemether +Croscarmellose

A 1:1 mixture of artemether and crospovidone was prepared, and the same procedure was used for other drug-excipient combinations. These mixtures were then analyzed with an FTIR spectrophotometer, which recorded their IR spectra in the range of 4000 to 400 cm⁻¹.

Differential Scanning Calorimetry (DSC):

Fig. 9: Pure drug Artemether

Fig. 10: Artemether + Excipients

The preparation's thermal behavior was analyzed using DSC to determine its melting point, crystallinity, breakdown, and drug-excipient interaction. The compatibility of Artemether and all excipients is demonstrated by their DSC, with the latter showing a noticeable endothermic peak at 86.94°C at 5.18 minutes.

Saturation solubility studies for drug:

Table 5: Artemether pure drug in various non-volatile solvents

Solvent	Solubility (mg/ml)
PEG 200	22.30±2.01
PEG 400	32.50±3.20
Propylene Glycol	25.38±3.35
Tween 80	28.20 ±2.04
Tween 20	23.80 ±1.56

Saturation solubility tests were conducted to determine Artemether's solubility in various non-volatile solvents. The results revealed that Artemether had the greatest solubility in PEG 400, with a value of 32.50±3.20 mg/ml.

Evaluation result of Tablet:

Table 6: Evaluation result of Liquisolid Tablet

Formulation	Weight variation (%)	Hardness (kg/cm2)	Thickness (mm)	Friability (%)	Disintegration time (min)
TF1	202.4±1.54	3.40±0.05	2.80±0.10	0.45±0.08	18±0.07
TF2	205.2±1.20	3.26±0.10	2.90±0.18	0.43±0.04	8±0.05
TF3	201.8±1.58	3.22±0.07	2.73±0.25	0.44±0.06	12±0.04
TF4	200.6±1.63	3.20±0.15	2.60±0.15	0.36±0.02	5±0.03
TF5	206.2±1.18	3.45±0.10	3.10±0.10	0.41±0.10	8±0.08
TF6	204.10±1.66	3.30±0.18	2.71±0.05	0.42±0.06	10±0.01
TF7	202.15±1.53	3.25±0.14	2.76±0.08	0.44±0.15	14±0.28
TF8	198.56±1.80	3.15±0.20	2.50±0.20	0.40±0.02	16±0.05

Drug content:

Table 7: Liquisolid Tablet Drug Content

Formulation	Drug Content
TF1	95.91±0.05
TF2	97.20±0.08
TF3	98.40±0.04
TF4	99.86±0.02
TF5	95.16±0.40
TF6	96.74±0.01
TF7	97.80±0.10
TF8	96.20±0.15

According to Table 7, the drug content ranges from 95.16% to 99.86%. The findings show that the methods used in this investigation to create the liquisolid compact were able to create a formulation with a consistent amount of medication.

In vitro Dissolution study:

The dissolving rate of both the pure medication Artemether and the liquisolid tablet was evaluated using the IP Monograph of the Artemether tablet. The results showed that the liquisolid tablet usually dissolved at a significantly higher rate than the powdered drug when a non-volatile solvent was introduced (Table: 8).

Table 8: Cumulative % Drug release of Liquisolid tablet

% Drug Release	0	5	10	15	20	25
TF1	0.00	42.40±1.06	57.17±0.02	65.22±0.20	78.15±1.15	89.29±1.40
TF2	0.00	38.62±1.08	55.43±0.25	64.05±1.05	71.32±1.17	86.20±1.10
TF3	0.00	43.15±1.32	52.60±1.12	66.21±0.40	78.27±1.28	93.49±1.32
TF4	0.00	44.18±1.07	58.35±0.08	71.21±0.05	84.80±1.25	98.89±0.22
TF5	0.00	39.29±0.02	50.68±1.18	64.25±1.25	76.62±0.08	89.33±1.10
TF6	0.00	43.07±0.05	53.67±0.09	74.55±1.02	82.70±0.08	94.20±1.04
TF7	0.00	36.05±1.15	48.38±0.40	59.70±1.28	72.87±1.18	86.33±1.12
TF8	0.00	40.12±0.08	52.17±1.14	63.20±1.20	79.30±1.04	92.28±1.22

Fig. 11: % Drug release of tablet formulations

Analysis of Data:

It was found that Crospovidone, SSG, and Croscarmellose Sodium positively impacted drug release when the effect of these factors on % drug release (Y1) was analyzed using a polynomial equation. A 3D response surface plot helped visualize how these superdisintegrants influenced Artemether release. The response curve for Y1 showed a clear increase in drug release as the concentrations of SSG, Croscarmellose Sodium, and Crospovidone were raised from 4 mg to 8 mg, suggesting that higher amounts of these excipients improve the drug's release rate.

Fig. 12: Contour plot of % drug release

Fig. 13: 3D Response Surface Plot

The impact of independent variables on friability (Y2) was assessed using a polynomial equation, which revealed that Crospovidone, SSG, and Croscarmellose Sodium negatively affected friability. A 3D response surface plot demonstrated that as the concentrations of these excipients increased from 4 mg to 8 mg, there was a clear reduction in friability. The statistical model identified the eighth formulation run as the most optimized, achieving a high drug release rate of 96.89% and low friability of 0.36%, indicating improved tablet strength and performance.

Fig. 14: Contour plot of friability

Fig. 15: 3D Response Surface Plot

CONCLUSION AND DISCUSSION:

This study showed that Artemether, a poorly water-soluble antimalarial medication, may be made more soluble and dissolve more quickly using the liquisolid compact approach. The drug was effectively turned into a dry, free-flowing, and compressible powder by replacing Mannitol with Aerosil 200 for the coating and carrier materials, and using PEG 400 as the liquid vehicle. Due to the optimal disintegrant combination, F4 demonstrated the most constant and quick drug release among the studied formulations, with a 25 minute half-life. While FTIR and DSC experiments revealed that Artemether and excipients were compatible, evaluation of pre- and post-compression characteristics confirmed good flowability, tablet uniformity, and mechanical strength. All things considered, the liquisolid method provides an easy, affordable, and expandable way to increase Artemether's bioavailability.

ACKNOWLEDGMENTS:

In order to complete this experiment, the author would like to thank Loknete Dr. J. D. Pawar College of Pharmacy, Manur (Kalwan) for supplying the necessary components and lab equipment.

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Received on 12.07.2025 Revised on 04.10.2025

Accepted on 08.12.2025 Published on 06.07.2026

Available online from July 20, 2026

Asian J. Pharm. Res. 2026; 16(3):229-236.

DOI: 10.52711/2231-5691.2026.00034

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Ratio (Carrier: Coating)	10:1	10:1	10:1	10:1	10:1	10:1	10:1	10:1
LF	2	2	2	2	2	2	2	2