INTRODUCTION:

Oral medicine delivery systems have captured the majority of the worldwide drug delivery manufacturing since they are the most affordable. This oral route could be difficult for pharmacological substances with weak solubility in water.^1,2 The inability of around 40% of novel chemical entities to dissolve in water offers a substantial challenge to current medicine delivery technology.^3,4 In this regard, SEDDS have proven to be an effective drug delivery technique for overcoming restrictions associated with poorly bioavailable medicines by increasing surface area.⁵

Anthelmintic medications are prescribed to treat worm infections. Praziquantel helps by producing severe spasms and muscle paralysis in the worm. This paralysis is accompanied by, and most likely caused by, a fast Ca2+ influx within the schistosome. Praziquantel is an anthelmintic medication used to treat schistosome, tapeworm, and other fluke infections.

PZQ dissolves readily in methanol and dichloromethane. In 2010, WHO suggested that preschool-aged children be included in large-scale treatment schemes.⁶ Praziquantel is the medication preferred for treating all schistosoma infections.⁷ SMEDDS can increase medication absorption by improving diffusion and drug solubility, protecting against enzymatic hydrolysis, increasing intestinal lymphatic drug transport and inhibiting P-glycoprotein efflux. This study is primarily concerned with the development of a PZQ-loaded SMEDDS suitable for oral delivery to patients.^8,9

MATERIALS AND METHODS:

Praziquantel was donated by Microlab Pvt. Ltd. Goa, Oleic acid and Cremophore RH 400 was obtained from Chemdyes Corporation & PEG 400 was obtained from Molychem.

Methods:

FTIR Analysis:

Infrared ranges of PZQ with Fourier Transform Infrared Spectrophotometer by using the KBr pellet method and scanned in the 4000 to 400cm1 range.

Solubility study:

PZQ was tested for solubility in a number of oils, as well as in surfactants, including Cremophore RH 40, Tween 20, Span 20 and Tween 80. 2ml of the necessary solvent and extra amount of drug were put into a vial. It was held in orbital shaker for 72 hours and then retained 24hours to reach equilibrium. The resulting mixture was then centrifuged for 30 minutes at 5000rpm. After that previous combination had been diluted with the necessary amount of methanol, filter it. Using a UV visible spectrophotometer, the PZQ's solubility was evaluated at 263nm.^10,11,12

Preliminary screening of surfactants:

Surfactant and oil have been combined in a 1:1 ratio (300mg Cremophore RH 40, Tween 80, Tween 20, and Span 20 were added to 300mg oily phase).^13,14

Preliminary screening of Co-surfactants:

Several co-surfactants (PEG 400 and Propylene glycol) have been evaluated utilising the selected oily phase and surfactants at a ratio of 3.2:1.^15,16,17

Preparation of Pseudo-ternary phase diagram:

The preliminary screening of surfactants and co-surfactants and solubility tests, oleic acid was chosen as the oil phase, Cremophore RH 40 as the surfactant, and PEG400 as the co-surfactant. Three components contained 100% concentrations of oil, Smix, and water. Oil and Smix were incorporated at ratios of 1:9, 2:8, 3:7, 4:6, 5:5, 6:4, 7:3, 8:2, and 9:1 to achieve the desired (Smix) value (1:1, 2:1, and 3:1). The Design-Expert® tool (version 13) was used to provide responses to all model formulations.^18,19

Preparation of liquid self-microemulsifying formulation with praziquantel:

Praziquantel was added in varying percentages to combinations of oil and Smix afterwards a suitable quantity of water was incorporated into the mixture drop by drop with steady stirring on a magnetic stirrer. Stirring the solutions resulted in the formation of microemulsions containing praziquantel. Each of the formulations were kept at the proper temperature.²⁰

Characterization of formulations:

Appearance study:

Each optimised batch's created self-microemulsion was visually assessed. The observed colour, character, and texture of each formulation along with its specification were noted in the results and discussion.

Percentage transmittance:

The transmittance of the solution was measured by using a UV Spectrophotometer.

Cloud point determination:

The cloud point is the moment in time when there is cloudiness.

Viscosity:

This was performed with a Brookfield Rheometer.

Particle size analysis:

The Zetasizer is used to determine particle size.

Determination of zeta potential:

This method includes formulation of dispersion of microemulsion. Then this dispersion is fill in the zeta cell and placed in Zetasizer for determination of zeta potential and interpreted in result.

In-Vitro drug release:

The in-vitro drug release was analyzed in 900 ml (0.1 N HCL) at 37⁰+5⁰c by a USP type-II dissolving test apparatus. At 2, 5, 10, 15, 20, 25, 30, 45, and 60 minutes.^21,22

Statistical analysis:

Statistical optimisation technique was carried out with the use of optimisation software such as Design Expert Software. Multiple regression analysis and ANOVA were used to analyse all four answers, namely % transmittance, cloud point, viscosity, and self-micro emulsification time.^23-26

RESULT AND DISCUSSION:

This study aimed to determine how self-micro emulsifying formulations affected praziquantel solubility and bioavailability.

Appearance study:

The appearance study of all formulation as shown in table no. 1.

Table 1. Appearance study of all formulation

Formulation Batches	Colour	Texture
F1	White	Transparent
F2	White	Transparent
F3	White	Transparent
F4	White	Transparent
F5	White	Transparent
F6	White	Transparent
F7	White	Transparent
F8	White	Transparent
F9	White	Transparent

FTIR:

The pure drug Praziquantel exhibited sharp peak at 3287.07 cm−1, 3003.59 cm−1, 2925.48 cm−1, 1630 cm−1, 1443.46 cm−1, 1350 cm−1 and 1126.22 cm−1 indicating the presence of O-H stretching, C-H stretching aromatic, C-H stretching alkyl, C=O stretching, C-C aromatic, C-N stretching and C-H bending, which confirms and identifies the drug when compared with the standard spectra of Praziquantel as shown in figure 1.

Fig. 1 FTIR Spectra of PZQ

Solubility study:

The graph of solubility of praziquantel are given below in Fig.2 & 3.

Fig. 2 Solubility graph of PZQ

Fig. 3 Solubility graph of PZQ in Smix

Oleic acid chosen as the oil phase with maximum solubility (19.227+0.12mg/ml) out of all the vehicles tested. As a surfactant and a co-surfactant, respectively, Cremophore RH 40 (20.251+0.55mg/ml) and PEG 400 (15.14+0.14mg/ml) were chosen.

Preliminary screening of surfactant:

In present study, the highest % transmittance is acquired by the following order Cremophore RH40 > Tween 80 > Tween 20 > Span 20. The Cremophore RH 40 shows the highest transmittance value while Span 20 shows lowest value which is shown in Fig. 4

Preliminary screening of co-surfactant:

It was stated that the co-surfactants PEG 400 and Propylene glycol have been compared. Oleic acid and Cremophore RH 40 demonstrated good % transmittance with the above co-surfactant. PEG 400 has high percentage transmittance i.e., 80.60 % and Propylene glycol has 70.14% which is shown in Fig.4.

Fig. 4. % Transmittance of selected Smix

Preparation of Pseudo-ternary phase diagram:

Water titration used to generate the pseudo-ternary phase diagram, which is illustrated in figures 5(a), 5(b), and 5(c). The darker area represents the microemulsion zone, whereas the larger area represents stronger self-microemulsifying ability.

Fig. 5 (a) Pseudo-ternary phase diagram of Oil, Smix & water (1:1)

Table 2. Characterization of PZQ SMEDDS formulation

Batch	% Transmittance	Cloud Point (⁰c)	Viscosity (mpas)	Average globule size (nm)	Zeta potential (mV)
F1	90.2±0.55	79.01±1	1.66± 0.29	495±0.5	-16.2±0.6
F2	89.1±0.6	65.21±0.5	1.24± 0.36	485.1±0.6	-15.3±0.28
F3	85.20±0.26	70.12±0.5	1.48± 0.26	301.3±1	-17.1±0.41
F4	93.5±0.5	63.1±1	1.55± 0.51	322±0.3	-2.8±0.51
F5	98.021±0.29	85.3±1	1.85± 0.41	282.7±0.2	-23.9±0.45
F6	94.17±0.41	72.21±0.5	1.23± 0.66	292±1	-15.9±0.22
F7	83.3±0.6	63.4±1	1.57± 0.45	345±0.5	-10.5±0.41
F8	95.17±0.3	83.2±0.5	1.46± 0.3	298±0.3	-9.8±0.51
F9	84.67±0.2	78.1±1	1.14± 0.55	312±0.4	-14.2±0.34

Data Expressed as mean ± SD (n=3)

Fig. 6 Globule size of F5 formulation

Fig. 7 In-vitro drug release of F1-F9

CONCLUSION:

In this study, self-microemulsion of Praziquantel was prepared. The excipients such as oil (Oleic acid), Surfactant (Cremophore RH 40), Co-surfactant (PEG 400) were selected on solubility study. Preliminary screening of Smix showed more than 95% of transmittance. The prepared formulations showed cloud point above 63.1⁰c. Globule size of optimize formulation was found to be 282.7 nm which enhance penetration efficiency of drug and % drug release was found to be 91.32%. We observed that created SMEDDS increased solubility, oral bioavailability, and therapeutic application of PZQ as an anthelmintic drug.

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Received on 17.02.2024 Revised on 11.05.2024

Accepted on 18.07.2024 Published on 20.01.2025

Available online from January 27, 2025

Research J. Pharmacy and Technology. 2025;18(1):227-231.

DOI: 10.52711/0974-360X.2025.00035

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