Formulation And Evaluation of Dexketoprofen Trometamol Loaded Microsponge Gel

Abstract

Objective: The research work aims to demonstrate the potential of this microsponge gel as an effective treatment for severe acute pain with improved drug delivery and therapeutic outcomes. The research work involves the formulation and characterization of a Dexketoprofen Trometamol loaded microsponge gel for the severe acute pain. Microsponges are introduced as a promising drug delivery system due to their ability to provide sustained drug release and improved skin permeation with increased stability and its use in a microsponge gel formulation is hypothesized to improve its efficacy. Method: Microsponge loaded with Dexketoprofen trometamol were successfully formulated by quasi-emulsion solvent diffusion method. The dosage form was formulated by the organic phase containing drug and solvent (ethanol) with polymer (1-5% w/v) and outer phase containing water with surfactant (PVA) (0.1-1%w/v). The internal phase was added drop-wise to external phase with high speed continuous stirring that formulate porous microsponge after evaporation. The polymers used were ethyl cellulose and Eudragit L100. Result: Thus total 8 formulations were prepared with different polymer, surfactant and solvent combinations. It was observed that the among 4 formulation containing ethyl cellulose as polymer the formulation F2 showed lowest particle size of 09µm and greater drug content (59.14%), larger drug entrapment efficiency (60.85%) and a better spreadability of 9.20g.cm/sec, and formulation F6 showed least particle size(12µm) and better drug content, drug entrapment efficiency ( 61.24%, 59.10%, respectively), and a better spreadability of 9.12g.cm/sec. among both F2 and F6, F2 could be considered as a better formulation.Conclusion: In this study it was founded that microsponge had a greater stability among wide temperature range and shows better drug loading capacity and good spreadability that might be used for sustained release formulation.

Keywords

Introduction

Microsponges are spherical, porous, microscopic particles. These are polymeric delivery system and a drug carrier which have tiny microscopic structure with a larger porous surface. These are micro-sized particle with average diameter of 5-30 microns ¹. Microsponge have unique compression and also have a unique dissolution due to its spongy structure ^2.Microsponge can deliver drug at minimal amount of dose and work efficiently in enhancing stability, modifying drug release and reducing side effects ^3. These have flexibility to entrap a wide range of active ingredients which are mostly used for prolonged topical administration for extended release of drug ^4. Recently, In oral drug delivery microsponge shows increase rate of solublization of poorely water soluble drug ^5. As the pores are very small containing about 2,50,000 pores in a typical 25 micrometer microsphere. ^6. A 25 micrometer sponge may have internal pore structure equal to 10ft length, making it almost 1ml/gram for drug retention ^7.

Figure 01: - Structure of microsponge

HISTORY OF MICROSPONGE

The technology of microponge was developed by won in 1987 and the original patent was assigned to Advanced Polymer Systems Inc.^8. The company worked on many variations of this technique and the technique was applied to various cosmetics as well as OTC and prescription drug ⁹and also in some FDA-approved products such as- Retin A Micro^® (0.1/0.04% tretinoin) and carac (0.5% FU) ^10.

CHARACTERISTICS OF MICROSPONGE^{11, 12, 13}

Figure 01: - Chart showing characteristics of microsponges ²⁶

ADVANTAGES OF MICROSPONGE^{14, 15, 16, 17}: -

MECHANISM OF DRUG RELEASE FROM MICROSPONGE:

Figure 03: - Chart showing Mechanism of drug release from Microsponge drug delivery system ²⁶

MATERIAL AND METHOD

Table no 01:- Formulation design of various Dexketoprofen trometamol microsponge formulations

• Particle size determination
• Ph of formulation
• Morphology and surface topography
• Drug entrapment 
• Entrapment efficiency
• Thermal stability

5. Particle size determination ²⁰: -The mean particle size of Dexketoprofen trometamol loaded microsponge was determined using an optical microscope. The microscope was fitted with a stage micrometer to calibrate the eyepiece micrometer. The particle size of formulated cubosome was determined using microscopy. Simple microscope under 100x resolutions was used to determine size of the cubosome. The average particle size was determined using the following formula:

D?mean=∑nd∑n

 

5. pH of formulation ²¹: -The pH of formulation was determined by using ph paper. Firstly 1mg of formulation was dissolved in 10ml oh freshly prepared 7.4ph phosphate buffer or in normal distil water. The pH papers were dipped in all formulations and on the basis of ph meter the ph of formulations were noted.
5. Morphology and surface topography ²²:- For determination of morphology or surface morphology scanning electron microscopy(SEM) is used.

The sample was mounted directly on to the SEM sample holder using double sided sticked tape. The images were recorded at different resolutions. Surface topography and surface morphology was examined using high resolution scanning electron microscopy (HR-SEM) under resolution 100x to 5000x.

5. Drug content ²³: - To measure drug content in microsponge 100 mg of precisely weighted microsponge is mixed in 100 ml of 6.8 pH phosphate buffer. The mixture is filtered through 0.45 µm membrane filter and sample is analyzed at suitable wavelength using UV.

Drug content %=Actual amount of drugWeighed amount of sponge×100

5. Drug Entrapment efficiency ²⁴: - Drug entrapment efficiency is assessed through solvent extraction method.

10 mg of precisely weighed microsponge is dissolved in 5ml of methanol using magnetic stirrer for 20 min.

20 ml of freshly prepared PBS is added and heated at 45-50^oC .Till the formation of clear solution. Methanol is evaporated and cooled at 25^oC and filtered.

The drug concentration is measured by UV.

DEE %=Actual drug content of spongeTheoratical drug content of sponge×100

 

5. Thermal stability ²⁵: - The thermal efficiency of microsponge are analyzed by differentil scanning calorimetry (DSC). The DSC analysis was performed from temperature range of 0^oC to 600^oC and the effect of temperature was noted and graph was prepared to show chart of effect of temperature on enthalpy change of the formulations.

RESULTS AND DISCUSSION

Drug- Exepient interaction compatibility study of Dexketoprofen trometamol and Eudragit L100 and Ethyl cellulose before formulation of microsponge: -

The compatibility study of drug and excipient shows no interaction. The graph complies with the graph of standard graph of Dexketoprofen Trometamol. That shows no specific interaction between drug used and excipients used.

Figure 04: - FTIR spectrum of Dexketorofen trometamol ,Eudragit L100, Ethyl cellulose, Ethanol and polyvinyl alcohol

Evaluation of micrsponge:

    

Figure 05:- Optical microscopic image of Dexketoprofen trometamol loaded microsponge

Figure 06:- HR-SEM image of Dexketoprofen trometamol loaded microsponge under 50,000 x resolutions

Figure 07: - Bar graph showing mean particle sizes of various formulations of Dexketoprofen trometamol loaded microsponges

pH of formulations: - The ph of formulations found to be fall between 5.6-6.2, which showed that the microsponges were of slightly acidic in nature.

Figure 08: - Bar graph showing Ph of various Dexketoprofen trometamol microsponge formulations

Drug content: -The drug content of Dexketoprofen trometamol loaded microsponges was found to be in the range of 42.26-60.24%. When the concentration of polymer was increased, the production yield of microsponges was also found to be increased. This may be due to higher amount of polymer, thus resulting in an increase in total mass of the microsponges

Figure 09: -Percentage drug content of various formulations of Dexketoprofen trometamol loaded microsponge

Drug entrapment efficiency: -The drug entrapment efficiency of Dexketoprofen trometamol ranged from 42.14%-60.85%. The results of drug entrapment efficiency showed that, with increase in polymer concentration, the drug entrapment efficiency was also increased.

Figure 10: - Drug entrapment efficiency of Microsponge containing Dexketoprofen trometamol

Spreadability: -The spreadability of formulations were found between 8.22-9.20. The spreadability of formulation F2 showed better spreadability among ethyl cellulose formulations and formulation F6 showed better spreadability among Eudragit L100 containing formulations. While among all formulations F2 shows better spreadability.

Figure 11: - Bar graph showing Spreadability of various formulations of Dexketoprofen trometamol microsponges

S.No.	Formulation	Mean particle size(µm)	pH	%Drug content	DEE%	Spreadability (gm.cm/sec)
01.	F1	16	5.7	55.30	51.35%	8.50
02.	F2	09	6.2	59.14	60.85%	9.20
03.	F3	42	5.6	42.26	42.14%	8.22
04.	F4	23	5.7	48.40	46.07%	8.40
05.	F5	35	5.6	49.60	48.24%	8.84
06.	F6	12	6.0	61.24	59.10%	9.12
07.	F7	25	5.7	56.80	53.45%	8.65
08.	F8	21	5.8	58.24	55.80%	8.70

Table 03: - Table showing mean particle size, pH, %Drug content, DEE% and Spreadability of different formulations of Dexketoprofen trometamol loaded microsponge

Figure 12: - Bar Graph showing pH, mean particle size, % Drug content, DEE% and spreadability of various formulations of Dexketoprofen trometamol loaded micrsponge

ACKNOWLEDGEMENT

I dedicate my entire work to Mahadev ji and Maa shayar maihar wali mata, they were with me during entire research purpose. Some parameters of evaluation was directly supported by IIT BHU, Varanasi, I felt deeply thankful to the instrument in-charge of CIF, IIT, BHU, Varanasi. 

CONCLUSION

Microsponges are introduced as a promising drug delivery system due to their ability to provide sustained drug release and improved skin permeation. Dexketoprofen Trometamol is a NSAID drug used in some cases of acute pain and its formulation in microsponge hypothesizes that its entrapment efficiency is enhanced and there is also enhancement in its spread ability so that it may be easily used in topical formulations. These are valuable drug matrix substance with several beneficial advantages like having good physical, chemical and thermal stability and allow greater flexibility in dosage form manufacturing and drug entrapment.

Thus total 8 formulations were prepared with different polymer, surfactant and solovent combinations. It was observed that the among 4 formulation containing ethyl cellulose as polymer the formulation F2 showed lowest particle size of 09µm and greater drug content (59.14%), larger drug entrapment efficiency (60.85%) and a better spreadability of 9.20g.cm/sec, and formulation F6 showed least particle size(12µm) and better drug content, drug entrapment efficiency ( 61.24%, 59.10%, respectively), and a better spreadability of 9.12g.cm/sec. among both F2 and F6, F2 could be considered as a better formulation.

The application of microsponge showed a better drug entrapment efficiency, better drug content, most précised particle size which results in better spreadability that makes it easy for topical application and makes its available for drug delivery of various delivery systems like gels, paste and ointments etc. In this study it was founded that microsponge had a greater stability among wide temperature range and shows better drug loading capacity and good spreadability that might be used for sustained release formulation. Microsponge delivery system holds a promising future in various pharmaceutical applications in the coming years as they have unique properties like extended release, reduced irritancy, small size, self sterilize and compatible with most of vehicles and ingredients, so flexible to develop novel product forms. Thus, MDS is a very emerging field which is needed to be explored.

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