Preparation and in vitro Characterization of Diacerein Microsponges Loaded Topical Gels

The innovative medicine delivery system’s objective is to quickly carry the required drug concentration to the proper room in the body in a therapeutic amount (Figure 1). The medication should be delivered by the drug delivery system promptly. Throughout a predetermined treatment period, the body is in a regulated manner.¹

Figure 1:
Plasma Concentration. vs Time.

Two distinct systems can be used for novel drug delivery:

Sustained release medication delivery systems.
Controlled-release drug delivery system.

It is a medication dosage form intended to postpone the onset of a curative effect in order to maintain the plasma profile. For a extended period of time and the effect appears delayed in the systemic circulation. Its pharmaceutical activity frequently takes time to begin and its therapeutic effects last a sustained amount of time.¹

This system’s significance extends beyond the realm of prolonged pharmacological action; instead, it displays probability and repeatability in the kinetically of drug release. Drug release from a controlled release drug delivery system happens at a frequency profile that is predictable from one component to the next and kinetically likely.¹

Topical therapy is a targeted medication delivery approach that can be applied topically, subcutaneously, vaginally, or through the eyes. The main route for topical medicine delivery is the epidermis, which is also one of the human body’s easiest organs to apply cosmetically. Topical medications are applied to the skin for effects that are surface, local, or systemic in nature. The base’s medicinal qualities, such as its emollient, calming, or protecting function, may occasionally allow for its exclusive usage. The therapeutically effective components in many topical treatments are, however, dispersed or disintegrated into the foundation. A vast array of topical drugs that can be utilized for a variety of drug delivery and therapeutic procedures are made possible by the combination of active ingredients and substrates. Classification of topical therapies containing therapeutically active substances can be done according to composition (hydrophilic creams), physical qualities (suspension), or intended usage (liniments).In addition to being an important advance over conventional methods (creams, moisturizers, applications and pastes), These delivery methods have the power to improve efficacy and tolerability, boost patient acceptance (including the quality of life for those with dermatitis) and address other unmet needs in the market for topical dermatological.²

Gels are a more recent category of dosage forms that are created when large amounts of an aqueous or hydroalcoholic fluid are trapped in a network of irregular solid particles. These particles can be made of synthetic or natural organic polymers, inorganic chemicals like aluminum salts, or both. The sort of colloidal components and amount of liquid in the composition will determine the gel’s physical appearance. The majority of topical gels are made with natural polymers like carbomers, which provide the product a nice, glittery, transparent appearance and are simple to remove with water from the skin. Gels are semisolid liquid-rich two-component systems. In a typical polar gel, an organic or synthetic polymeric forms a three-dimensional matrix over anhydrous liquid.³

Single phase gels- Gels in which there are no visible barriers separating the particles from the liquid and biomolecules are uniformly distributed throughout the liquid.

Double phase gels- Gel material is made up of bubbles of little unique pieces known as the magma. (Magnesia milk).

Every day, a vast array of new pharmacological classes are being developed as pharmaceutical delivery technologies develop. For a drug to be successful under any circumstances, a novel medication release mechanism with computed predetermined ratios at various points of function must be developed.⁴ Most conventional dosage forms are unrefined and contain a number of disadvantages, including reduced bioavailability, stomach and skin irritation, unpleasant reactions and negative effects of the active components. These include tablets, capsules, creams, lotions and gels with quick release.⁵ Microsponges, which are similarly composed of collapsible structures loaded with an active medicinal component, are highly cross-linked, polymeric permeable microspheres with several interconnected gaps. Microsponges’ porous surface enables a range of active pharmaceutical compounds to be kept in and released in a variety of quantities at the unique absorption location. The continuous pattern of open pores in the microsponges, which varies in size, permits the medicine to be held inside and release at a controlled rate.⁶

This microsponges formulation has an active component that releases in a controlled manner. Medication delivery via microsponges involves the use of small, inactive spherical compositions that do not irritate the skin film. These combinations were developed to use the least amount of medication possible while delivering the active ingredients at the administration site.⁷ A scientist named Richard Won invented microsponges. The diameter of the bead ranges from 5 to 100 m. A human sin is about five microns in size on average. The skin is impervious to the everlasting spheres. The active chemicals encircled by the pores are progressively absorbed by the skin. The polymers used in the microsponges’ production are what allow them to form cages. The most often used polymers for manufacture are E-RS100, E-RS PO, E-S100, polyhydroxy butyrate and polyvinyl benzene.⁸

• Advantage of microsponge technology.^9–11
• The elegance of the product is enhanced.
• The microsponges have less toxicity.
• Increased stability and solubility of drugs.
• Microsponges enhance the active medicinal components’ bioavailability.
• The microsponges enhance product performance.

Preformulation studies related to drug (Table 3),
Solubility studies (Table 4),
Standard curve (Table 5, Figure 2),
Identification of pure drug, FTIR Analysis (Tables 6, 7),
Preparation of microsponges gel,
Evaluation of microsponges gel,
Physical properties,
pH,
Spreadability,
Viscosity,
Drug content,
Particle size,
Loading efficiency,
Production yield,
In vitro drug release study,
Evaluation of microsponges.

Figure 2:
Calibration Curve of Diacerein.

By calculating the initial weight of raw materials and the final weight of microsponges, one can calculate the percentage yield. The formula can be used to get the percentage yield.

Using spectrophotometry, the microsponges were identified (λ_max=255 nm). After dissolving 100 mg of DCN microsponges in 100 mL of phosphate buffer (pH 6.8), the sample was stored for the entire night. The real drug content in the microsponge was calculated and expressed. The following formula was used to determine the microsponges’ loading efficiency (%).

Figure 3:
Loading Efficiency Chart.

Using an optical microscope and a calibrated ocular and stage micrometer, the average particle size of Diacerein-loaded microsponges was ascertained. A cover slip was placed on a spotless glass slide that had a small amount of microsponges spread out on it along with a drop of liquid paraffin. In order to determine the average particle size, measurements 100 particles of each batch. d_av=Σ nd Æn Where, dav is the average diameter of particles (μm), n is a number of particles per group and d is the middle value (μm). IV.

A digital pH meter was utilized to ascertain the pH of the gel composition. After dissolving 1 g of gel in 100 mL of distilled water, it was kept for two hours. It was measured how acidic the formulation was.

Color matters when it comes to patient compliance. The produced gels were examined visually to ensure they were clear, colored and free of any particles.

1 g of microsponge gel was precisely weighed, dissolved in methanol and then sonicated for 10-15 min. The resulting mixture was then added to a one hundred millilitre volumetric flask using methanol. To reach a concentration within Beer’s range, 10 mL of this was pipetted out and diluted to 100 mL using methanol. The final dilution was made with distilled water. Using a blank gel that had been prepared in the same way as the sample, the absorbance was measured at 255 nm using a UV spectrophotometer.

The viscosity of the various gel compositions was measured at 25°C using a Brookfield viscometer with spindle no. 64 running at 100 rpm. Using a Brookfield viscometer, the optimal formulation’s viscosity was ascertained without dilution. (Model-LVDV-E). The Brookfield Viscometer is made comprised of a spinning spindle and a fixed cup. Rotating spindles of varying sizes are employed and submerged in the test substance. big size spindles (big diameter and surface area) are used for low-viscosity liquids, whereas small spindles (small diameter and surface area) are used for high-viscosity liquids. Turn the spindle inside the microsponge gel until the viscometer’s dial readout remains constant. For repeatable results, repeat this process three times.

Good spreadability is one of the requirements for a gel to satisfy the ideal attributes. This phrase is used to describe the area that gel spreads easily when applied to the skin or other affected area. The spreading value of a formulation also affects how effective it is as a medicine. Spreadability is measured in terms of the number of seconds it takes for two slides to separate from gel that has been positioned between them when a specific stress is applied. Better spreadability results from separating two slides in less time. The formula below was then utilized to determine spreadability:

Where, S=Spreadibility, M=Weight in the pan, L=Length moved by the glass slide, T=Time taken to separate slide completely.

The calibration curve of diacerein was prepared in DMA (N, N-dimethylacetamide).

It was investigated how the drug and the formulation’s excipients interacted. The following are the outcomes (Figures 4, 5, 6):

Figure 4:
FT-IR of diacerein.

Figure 5:
FT-IR of Diacerein and Ethyl Cellulose.

Figure 6:
FT-IR of Diacerein and Eudragit RS100.

Prepared Microsponges: Microsponges were prepared using Quasi emulsion solvent diffusion method (Figure 7).

Figure 7:
Microsponges.

Internal Phase: Diacerein (100 mg) and Ethyl cellulose (200 mg F1, 250 mg F2, 300 mg F3) / Eudragit RS 100 (200 mg F4, 250 mg F5, 300 mg F6) in Dichloromethane (20 mL).

External Phase: Polyvinyl alcohol in distilled water, (0.75% w/v).

After preparing the microsponges, the yield percentage was determined. They were discovered to be between 70.12% and 86.52%. It displays rising drug usage: The percentage yield rose with the polymer ratio.

The range of loading efficiency was 70.41 to 92.66%. The formulations F3 and F6 were determined to have the highest loading efficiency. This demonstrates that loading efficiency rose as the drug: polymer ratio grew.

The color, texture and appearance of the obtained gel formulations of diacerein microsponges were examined visually. Each created formulation had a smooth texture, was yellow and exhibited good homogeneity-no lumps or syneresis-as well as viscosity.

The value of spreadability of microsponges F1 and F2 was found to be 7.4 and 5.0 g.cm/sec respectively, indicating the acceptable spreadability of gel.

Microsponge formulation F1 was found to be more viscous than the gel loaded with microsponge using Eudragit RS 100.

Using PBS (pH 7.4), the in vitro diffusion was done for the formulations F1 and F2 over a 12-hour period. At the end of the 12-hour period, formulation F1 was found to have more drugs diffused than the formulation F2, with percentages of 89.40% and 92.18%, respectively. As a result, the microsponge loaded gel formulation F1 was refined to provide regulated drug release with all desired characteristics.

Figure 8:
Cumulative % release vs time.

Diacerein was chosen as a model drug for MDDS to address these issues and enable controlled drug release because it has a short half-life and is poorly soluble in water. Using the polymers Eudragit RS 100 and Ethyl cellulose, diacerein is prepared as microsponges by the quasi-emulsion solvent diffusion process, which is then incorporated into gels. Compatibility studies were performed for drug and excipients.

A physical compatibility investigation revealed that there was no physical conflict between the medicine and the excipients.

An analysis of chemical compatibility (FT-IR) was conducted. There was no evidence of a drug-excipient interaction.

A standard graph was created for Diacerein and it was discovered that the solutions adhered to Beer Lambert’s law and demonstrated linearity (
R²=0.998).

Diacerein Microsponges were made using two different polymers to see which one best delay the release.

For every formulation, the in vitro release procedure was completed. Therefore, F2 and F4 were selected as optimized formulations.

We are thankful to SGRR University for providing the research facilities, also we are grateful to Department of Pharmaceutics, SGRR University for helping us in designing this novel research work.