Formulation And Evaluation of Betamethasone Valerate Coal Tar Emulgel for Treatment of Psoriasis

The skin is the largest organ of the human body, serving as a vital connection to the external environment. However, it is susceptible to various chronic conditions, one of the most prevalent being psoriasis. This section provides a comprehensive overview of psoriasis, its risk factors, and treatment options, followed by an introduction to the novel emulgel drug delivery system, which serves as the foundation for this research.  

Psoriasis: A Chronic Skin Disorder

Psoriasis is a persistent autoimmune skin illness characterized by the rapid overproduction of skin cells, leading to the formation of thick, scaly, and red plaques. It affects approximately 2 to 3% of the global population and is considered a moderately frequent dermatological disease. While its exact cause remains unknown, it is believed to result from a combination of immune system, environmental, and genetic factors. Psoriasis can appear anywhere on the body, but it most frequently affects the elbows, knees, scalp, and lower back. Beyond its physical symptoms, the condition can significantly impact a person's quality of life, leading to self-consciousness, social stigma, and psychological distress. It also increases the risk of other health issues, such as psoriatic arthritis and cardiovascular disease.  

Types of Psoriasis

Psoriasis manifests in several different forms, each with unique characteristics:

• Plaque Psoriasis (Psoriasis Vulgaris): The most common type, accounting for approximately 80% of cases. It is characterized by raised, red patches covered with silvery-white scales, known as plaques.  
• Palmoplantar Psoriasis: Primarily affects the palms of the hands and soles of the feet, causing painful thickening, scaling, and redness.  
• Guttate Psoriasis: Appears as small, drop-like, red lesions, often triggered by a bacterial or viral infection.  
• Inverse Psoriasis: Affects skin folds in areas like the armpits and groin, appearing as smooth, red, inflamed patches that are aggravated by sweating.  
• Pustular Psoriasis: Characterized by white, pus-filled blisters on red, inflamed skin. This form can be localized or widespread and, in its generalized form, can be life-threatening.  
• Erythrodermic Psoriasis: A rare but severe type that covers the entire body with a red, peeling rash, disrupting the body's ability to regulate temperature.  
• Nail Psoriasis: Causes changes in the nails, such as pitting, discoloration, and thickening.  
• Psoriatic Arthritis: A related condition that causes inflammation and joint pain, affecting individuals who have psoriasis.

Risk Factors and Triggers

The onset of psoriasis is influenced by a combination of genetic, environmental, and immune system factors. Key risk factors include a family history of psoriasis, immune system dysfunction, and environmental triggers such as infections, stress, and skin injuries. Other contributing factors are smoking, excessive alcohol consumption, and obesity. Hormonal changes and certain medications (e.g., lithium, beta-blockers) can also trigger or worsen symptoms.  

Treatment Options for Psoriasis

While there is no known cure, a variety of therapeutic options exist to manage psoriasis symptoms and improve quality of life. These treatments are often tailored to the individual and can include:

• Topical Treatments: The first-line treatment for mild to moderate psoriasis, including corticosteroids, topical calcineurin inhibitors, vitamin D analogues, salicylic acid, and coal tar.  
• Phototherapy (Light Therapy): Controlled exposure to ultraviolet B (UVB) or ultraviolet A (PUVA) light can be effective for many types of psoriasis.  
• Systemic Medications: Oral or injectable drugs like methotrexate, cyclosporine, and biologics are used for moderate to severe cases by suppressing the immune system.  
• Lifestyle and Self-Care: Techniques such as moisturizing, stress management, and avoiding personal triggers can help manage the condition.  

Introducing Emulgel: A Novel Drug Delivery System

Emulgel is a unique semi-solid pharmaceutical formulation that combines the properties of an emulsion (a mixture of oil and water) and a gel. This innovative system is designed to provide improved drug delivery, enhanced stability, and ease of use, making it suitable for topical applications in dermatology, including the treatment of psoriasis.  

The emulgel for psoriasis treatment offers several key advantages:

• Dual Mechanism of Action: The emulsion component enhances the solubility and skin penetration of active ingredients like Betamethasone Valerate, while the gel matrix provides stability, a cooling sensation, and makes the formulation easy to apply and spread evenly.  
• Improved Absorption: By combining these properties, emulgels can enhance the absorption of active ingredients into the skin, increasing the effectiveness of the treatment.  
• Enhanced Patient Compliance: Emulgels are less greasy than many conventional topical formulations and have a smooth texture that is easy to spread and non-staining, which contributes to better patient adherence to long-term treatment.  
• Controlled Drug Release: Emulgel formulations can be designed to release the medication gradually over an extended period, which can reduce the frequency of administration and improve patient convenience.  

The rationale for developing a Betamethasone Valerate and Coal Tar emulgel is to leverage these benefits to create a more effective, patient-friendly, and comprehensive treatment for psoriasis.

MATERIALS AND METHODS

The emulgel formulation and its subsequent evaluation were conducted using a systematic and well-defined methodology to ensure product quality and efficacy. The study began with the strategic selection of materials, followed by a detailed formulation process and a series of comprehensive evaluation tests.

Rationale for Material Selection

The selection of materials for the emulgel formulation was based on their specific therapeutic functions and compatibility with the final product. Betamethasone valerate was chosen as the active pharmaceutical ingredient due to its potent anti-inflammatory and immunosuppressive properties, which are highly effective in mitigating the symptoms of psoriasis, such as inflammation, redness, itching, and scaling. Its incorporation into the emulgel base ensures targeted delivery to the affected areas, thereby minimizing systemic exposure and associated side effects.    In a synergistic approach, coal tar was included for its keratolytic and anti-inflammatory effects. This dual-action ingredient helps to slow the overproduction of skin cells in psoriatic plaques, providing a more comprehensive treatment strategy that not only controls inflammation but also inhibits cell proliferation. The emulgel base itself was utilized to combine the properties of an emulsion and a gel, offering improved drug penetration, controlled release, and enhanced patient compliance, which directly addresses the limitations of conventional topical medications.    Among the excipients, olive oil was specifically chosen as the oil phase and permeation enhancer, as pre-formulation studies revealed it to be the most soluble solvent for betamethasone valerate. Tween 80 and PEG 400 were selected as the surfactant and co-surfactant, respectively, to stabilize the oil-aqueous interface and create a homogeneous emulsion. Carbopol 940 was employed as the gelling agent to provide the desired viscosity and structural integrity to the final formulation.

Comprehensive List of Materials and Equipment

The materials and equipment used for the formulation and evaluation process are listed below.  

• Materials:
  • Betamethasone Valerate, Olive Oil, Tween 80, PEG 400, Carbopol 940, Propyl Paraben, Methyl Paraben, Water.
• Equipment:
  • Digital Balance (Shimadzu AU220, Japan), High-Speed Homogenizer (Omni PDH, Omni International, USA), Probe Sonicator (Frontline, Model No. SS-100), Shaker Incubator (Equitron, India), UV-1800 Spectrophotometer (Pharmaspec 1800) (Shimadzu Co., Japan), Digital pH Meter (Elico, L1 612, India), pH Meter (Lab-India), FT-IR (Cary-630, Agilent), DSC (DSC-60, Shimadzu Co.).

Methodology: Formulation, Optimization, and Evaluation

The study began with a series of pre-formulation studies to determine the physical and chemical properties of the drug substance (API). This included evaluating the organoleptic properties of the drug and studying the solubility of Betamethasone Valerate in various solvents and excipients to select a suitable oil phase and emulsion system. The solubility studies confirmed that Betamethasone Valerate was most soluble in olive oil (26.8 mg/ml) and Tween 80 (25.23 mg/ml), which justified the selection of these components as primary formulation materials.  

The emulgel was prepared via a two-stage process:

1. Emulsion Preparation: The oil phase and aqueous phase were weighed and heated separately to a predetermined temperature. The heated oil phase was then slowly and continuously added to the heated aqueous phase while homogenizing to create a homogeneous emulsion.  
2. Emulgel Preparation: In a separate container, the gelling agent was dispersed in water. The prepared emulsion was then added to this gel dispersion with continuous stirring until a homogeneous emulgel was developed.  

To optimize the emulgel formulation, a 23 factorial design was employed to systematically evaluate the effects of multiple factors and their interactions on the final product's performance. The independent variables were the concentrations of oil (X1), S-Mix (X2), and the gelling agent (X3). The dependent variables evaluated were the formulation's viscosity (Y1) and drug content (Y2).

The final optimized emulgel batch was evaluated based on a number of parameters to ensure its physico-chemical properties, stability, and performance. These included pH measurement, viscosity measurement, Spreadability measurement, extrudability and washability, % drug content, and in-vitro diffusion studies to assess drug release kinetics.

RESULTS AND DISCUSSION

Characterization of the Active Pharmaceutical Ingredient (API) Betamethasone Valerate was identified as a white, odourless powder. Spectrophotometry analysis revealed a maximum absorption peak (λmax?) at 245-249 nm in methanol, which is close to the authentic wavelength reported in the literature. A calibration curve prepared in methanol + phosphate buffer (pH 7.4) showed a high correlation coefficient of 0.9989, demonstrating the linearity and accuracy of the analytical method used in the study. FT-IR analysis confirmed the characteristic functional groups of Betamethasone Valerate, including the C=O stretching at 1600.09   cm−1.

Optimization and Physico-chemical Evaluation

The factorial design indicated that Formulation F5 achieved the most desirable overall properties, exhibiting a high drug content of 91.3% and the highest viscosity (254.8 cP) and spreadability (8.1 g.Cm/sec) among the formulations. This suggests a non-Newtonian, possibly thixotropic, behaviour, which is desirable for a topical product that is stable in a container but spreads easily upon application. Additionally, F5 demonstrated "Excellent" washability and extrudability, which would enhance the patient's usage experience.

In-vitro Drug Release Studies In-vitro drug release data validated the Emulgels performance, with F5 demonstrating the highest cumulative drug release of 82.65% after 300 minutes, indicating a sustained and effective delivery of the medication. This result is directly related to F5's optimal component ratio, which enables a controlled release profile.