Pruritus, commonly known as itching, represents one of the most prevalent and distressing dermatological symptoms affecting millions of individuals worldwide. It is associated with numerous skin conditions including eczema, psoriasis, allergic dermatitis, and xerosis, significantly compromising patients' quality of life through sleep disturbances, psychological distress, and reduced daily functioning. The global market for anti-itch products continues to expand, driven by increasing prevalence of inflammatory skin disorders and growing consumer preference for safe, effective topical treatments^1-3. However, conventional anti-pruritic formulations often present limitations including adverse effects from prolonged use of corticosteroids and antihistamines, poor skin penetration of active ingredients, potential for skin sensitization from synthetic additives, and inadequate patient compliance due to greasy textures or inconvenient application methods. These challenges have intensified the search for alternative therapeutic approaches that combine efficacy with safety, particularly formulations derived from natural sources^4-6.

The therapeutic value of botanical oils for dermatology has been appreciated for millennia by various medical traditions. Black seed oil from Nigella sativa L. (Family: Ranunculaceae) stands out as a noteworthy candidate for anti-inflammatory as well as anti-pruritic uses^7-12. Black cumin or kalonji, as black seed is also called, produces seeds containing high levels of bioactive phytochemicals, with thymoquinone being its main pharmacologically active compound, accounting for about 30-48% of the essential oil content. Besides thymoquinone, its oil contains therapeutically significant components such as thymohydroquinone, thymol, carvacrol, α-pinene, and p-cymene, as well as fixed oil fractions like linoleic acid, oleic acid, and palmitic acid. Systematic pharmacological studies have efficiently established that black seed oil possesses outstanding anti-inflammatory effects by suppression of inflammatory mediators such as prostaglandins, leukotrienes, and cytokines. Its antihistaminic effect has been explained as mast cell stabilization with suppression of histamine release, which directly counters a major mechanism in pruritic perceptions. Beyond this, black seed oil shows antioxidant effects for skin cell protection from oxidation, antimicrobial effects during defense against typical skin pathogens, as well as its role as an immunomodulator for controlling excessive immune reactions in inflammatory skin conditions. Clinical, as well as experimental studies, supported its potency in controlling various inflammatory dermatoses, culminating in a firm scientific basis for its use as an active entity in contemporary topical preparations^13-20.

Calendula oil, which is obtained from flowers of Calendula officinalis L. (Family: Asteraceae), constitutes yet another plant-derived compound with established dermatological effects. For more than a century, calendula, or marigold, has been utilized in ancient forms of medicine for pruritus as well as skin inflammation to promote wound healing ^21-25. Calendula oil possesses a rich composition of bioactive compounds, such as triterpenoid saponins (specifically, oleanolic acid glycosides), flavonoids (quercetin, isorhamnetin, glycosides thereof), carotenoids (β-carotene, lutein), volatile oils (α-cadinol, τ-cadinol), as well as polysaccharides. This range of phytochemicals imparts numerous therapeutic effects that are applicable for pruritus relief. calendula possesses antimicrobial actions towards bacteria as well as fungi that are implicated in secondary skin infection, emollient as well as soothing effects that restore skin barrier integrity, as well as tissue repair-promoting effects. The formulation of black seed oil with calendula oil constitutes a rational multi-target pruritus management approach, also capable of conferring a mixture of therapeutical benefits with complementary mechanisms of actions that result in a likely resultant synergism ^26-28.

Although they hold promise as therapeutics, topical application of both oils presents major pharmaceutical challenges. They represent extremely lipophilic molecules with low aqueous solubility, which translates to poor penetration upon application in typical oil-in-vehicles formulations in dermatology. They are cosmetically unacceptable to most consumers due to their viscous texture, which presents a challenge to widespread application over affected dermatonal areas ^29-30. Furthermore, chemical instability of some of the bioactive structures upon exposure to light, air, or temperature fluctuations may detract from therapeutic performance during storage. Such shortcomings dictate sophisticated delivery systems that will bypass physicochemical impediments with retention of the intrinsic biological activity of the natural products ^31-32. Microemulsions are next-generation colloidal drug delivery systems that address challenges with topical delivery of lipophilic natural products. Conceptually, microemulsions are thermodynamically stable, transparent to translucent mixtures of oil, water, and surfactant, and often a co-surfactant. Microemulsions spontaneously form and have droplet sizes in the 10 to 100 nm range ^34-37. The nanoscale size significantly increases the surface area available for skin absorption, enhancing the capacity of active moieties to penetrate skin past the stratum corneum barrier. They are also thermodynamically stable and do not require continuous input of energy to maintain their thermodynamic stability like simple emulsions. In addition, lower viscosity and aesthetically pleasing appearance improve patient acceptability and patient compliance. Microemulsions have a high solubilization capacity for both lipophilic and hydrophilic compounds, while the surfactant component provides penetration enhancement by transiently disrupting the organization of stratum corneum lipids. The choice of surfactants for them in dermatological applications is important. Vegetable oil ethoxylates represent a new class of non-ionic surfactants that have excellent emulsifying capability and address risks around skin irritation and environmental risks associated with traditional synthetic surfactants ^38-39. They are made by the ethoxylation of fatty acids or alcohols from vegetable oils, which provides a renewability aspect to their origin along with excellent biocompatibility, biodegradability, improved emulsifying ability at lower concentrations, and alignment with consumer preference for 'green' products.

This work formulates new microemulsion formulations of black seed oil and calendula oil with environmentally friendly vegetable oil ethoxylates as surfactants for pruritus symptom relief. This work seeks to formulate thermodynamically stable microemulsions by optimizing surfactant concentrations, oil weight fractions, and component selections to obtain specified physicochemical characteristics. Aggregate-scale characterization involves measuring droplet size, polydispersity index, zeta potential, pH, viscosity, and refractive index, as well as short- and long-term stabilities under different storage conditions. This manuscript constitutes an important extension of green natural product pharmaceutical formulation by combining two therapeutically complementary botanical oils in a green surfactant-based formulation system. This formulated product may offer a safer, more efficacious, synthetic anti-pruritic product alternative while further developing sustainable, nature-based therapeutics. Results will provide significant contributions to pharmaceutical formulation science, natural product drug delivery, and skin therapeutics, with extension to application beyond pruritus management in other inflammatory skin diseases.

2. MATERIAL AND METHOD:

2.1 Materials:

Black seed oil (Nigella sativa L.) and calendula oil (Calendula officinalis L.) were procured from a local supplier. Two types of vegetable oil ethoxylates were used as surfactants in this investigation, Hydrogenated castor oil ethoxylate, Rapeseed oil ethoxylate. These surfactants samples were kindly donated by Rossari Biotech Ltd. (Mumbai, India) and were utilized without further purification. All chemicals and organic solvents used in the experiments were of analytical grade quality and used without purification, except where specified otherwise. Throughout all custodial procedures deionized water (conductivity < 1µS/cm) was used to avoid ionic interference to reproducibility.

2.2 Methods:

2.2.1 Physicochemical Characterization of Oils:

The following characteristics were systematically studied using standard pharmacopeial methods: Physical Appearance and Organoleptic Properties: A visual inspection was performed under natural light to examine color, clarity, and the presence of any particulate matter or phase separation. Specific Gravity, Acid Value, Peroxide Value, Iodine Value, Saponification Value; All the obtained values were critically compared to the literature-reported reference standards and pharmacopeial specifications to verify the purity, authenticity, and freshness of the oil samples.

2.2.2 Surfactant Characterization:

The emulsifying agents HCO-40 (Hydrogenated Castor Oil-40 EO), RSO-10(Rapeseed oil -15 EO), and RSO-20(Rapeseed oil -20 EO) were characterized by evaluating their physical appearance, specific gravity, hydrophilic-lipophilic balance (HLB) values, and Surace tension.

2.2.3 HLB Blend Preparation:

Surfactant blends with varying HLB values were prepared by mixing lipophilic and hydrophilic surfactants in calculated proportions. Two different surfactant systems were formulated using HCO-40 (Hydrogenated Castor Oil-40 EO) as the hydrophilic surfactant in combination with RSO-15(Rapeseed oil -15EO) and RSO-20EO (Rapeseed oil -20EO) as lipophilic surfactants to achieve the desired HLB values.

The proportion of each surfactant needed to achieve the desired HLB value was calculated using the following equation:

HLB blend = [(% Surfactant A × HLB_A)

+(% Surfactant B × HLB_B)] / 100

2.2.4 Construction and Analysis of Pseudo-Ternary Phase Diagrams:

Pseudo-ternary phase diagrams were produced using the aqueous titration technique at a temperature of 25°C± 1°C to identify the region for area of microemulsion formation. Binary mixtures of the oil phase (blend of black seed oil and calendula oil) and surfactant were produced in varying weight ratios from 1:9 to 9:1 (w/w). At every oil-surfactant ratio, deionized water was added drop-wise with gentle magnetic stirring until persistent turbidity was obtained and the microemulsion region was observed as the point of clear, thermodynamically stable systems. Optimized formulations were chosen based on clarity, phase separation, spontaneous generation, and ability to incorporate water.

2.2.5 Preparation of Microemulsion Formulations:

Microemulsion formulations (F1–F8) were prepared via spontaneous emulsification at room temperature. Accurate amounts of black seed oil, calendula oil, and the selected surfactant were combined and mixed under magnetic stirring (500rpm) for 10minutes to ensure a homogeneous oil-surfactant phase. Deionized water was then added in a dropwise manner with stirring until a clear transparent microemulsion was formed. Each formulation consisted of different oil-to-surfactant-to-water ratios, which were chosen from the microemulsion region of the phase diagram.

2.2.6 Physicochemical Evaluation of Microemulsions

The microemulsions were examined for visual appearance (clarity, color, and homogeneity), pH, and viscosity using a Brookfield viscometer at 25°C, and electrical conductivity using a digital conductivity meter to determine the type of microemulsion (O/W or W/O). Droplet size was assessed by dynamic light scattering by using a Malvern Zetasizer Nano ZS at 25°C.

2.2.7 Stability Studies:

The physical stability was assessed by performing three stress tests. In the centrifugation test, the samples were centrifuged at 3000rpm for 20minutes and examined for phase separation. In the freeze-thaw cycling test, the samples underwent 3 freeze/thaw cycles between 4°C to 45°C (24hours per cycle), and were assessed for visible changes, phase separation, pH change, and droplet size change. Accelerated stability testing was performed by storing the formulations at room temperature (25°C) and elevated temperatures (45°C) for 30 days. Samples at 0, 15 and 30days were assessed for visual appearance, pH, droplet size, droplet size, phase separation, Odor and color or changes. Formulations that exhibited only minimal changes (pH less than 0.5units, droplet size expanded less than 20%, no phase separation) were considered stable.

2.2.8 Formulation of Microemulsion-Based Itch Relief Spray:

The optimized microemulsion formulation was transformed into a spray system for topical delivery. The formulation was supplemented with glycerine (5%w/w) as a humectant to limit trans epidermal water loss, aloe vera extract (0.5%w/w) for its soothing and anti-inflammatory properties, and phenoxyethanol (0.5% w/w) as a broad-spectrum preservative. The active agents were added in succession to the microemulsion under slow magnetic stirring. The entire formulation was then subjected to homogenization using a high-speed homogenizer for 10min at 500rpm to enhance the uniform distribution of components. The homogenized spray formulation was filled into pre-sterilized spray containers fitted with mist spray actuators.

2.2.9 Evaluation of Itch Relief Spray:

The formulation of microemulsion-based itch relief spray was assessed for physical appearance and uniformity, including color, clarity, and phase uniformity, immediately after preparation and after 24 hours. The pH was measured with a calibrated digital pH meter, and the viscosity was measured with a Brookfield viscometer to verify amenable flow properties for the spray application. Centrifuge stability was assessed by exposing the formulations to 3000rpm for 20minutes followed by visual observation for any evidence of phase separation or other instability.

2.2.10 Sensory Evaluation of Itch Relief Spray:

Sensory panel of 10 evaluators was used to evaluate the subjective characteristics and acceptability of the spray. The following metrics were evaluated:

A) Non-Greasy Feel: is rated on a 5-point scale 1 = very greasy, 5 = completely non-greasy. This rating was assigned 5 minutes following application to the volar forearm.

B) Cooling Effect: is rated on a 5-point scale 1 = no cooling, 5 = very intense cooling. This effect is a measure of a user's immediate soothing sensation after spray is applied.

C) Ease of Spread: evaluated for smoothness of spreading and absorption rate (1 = difficult to spread/slow absorption, 5 = very easy to spread/very absorbent).

D) Overall Acceptability: a composite score that is a measure of the aggregate user experience satisfaction (1 = unacceptable, 5 = highly acceptable).

3. RESULTS:

3.1 Characterization of calendula oil and Black seed Oil:

Table 1: - Physicochemical parameters of oil.

Sr. No	Parameter	Black seed Oil	Calendula oil
1	Physical appearance	Light brownish yellow	Light yellow
2	Specific Gravity	0.912	0.918
3	Acid Value	1.86	1.23
4	Iodine Value	92.8	120
5	Peroxide Value	5.6	3.2
6	Saponification value	179.2	185

Table -5: - Microemulsion physical parameter

S. No	Formulation	Blend of oil	HLB	Microemulsion Type	pH	Density Kg/m3	ViscosityPS	Conductivity mS/m	Particle size nm
1	F-1	BSO 60 % and CO 40 %	11.4	O/W	6.58	1.035	32	385.5	143
2	F-2	BSO 80 % and CO 20 %	11.4	O/W	6.54	1.015	27	289.2	187
3	F-3	BSO 60 % and CO 40 %	11.7	O/W	6.75	1.020	37.8	269.3	150
4	F-4	BSO 80 % and CO 20 %	11.7	O/W	6.66	1.012	22.8	393.4	130
5	F-5	BSO 60 % and CO 40 %	12.4	O/W	6.78	1.020	33.6	246.4	157
6	F-6	BSO 80 % and CO 20 %	12.4	O/W	6.8	1.031	38.3	248.4	210
7	F-7	BSO 60 % and CO 40 %	12.8	O/W	6.24	1.034	41.20	270.4	170
8	F-8	BSO 80 % and CO 20 %	12.8	O/W	6.56	1.029	39.50	255.5	158

Figure 9 Sensory Evaluation of Itch Relief Spray Formulation 1

Figure 10 Sensory Evaluation of Itch Relief Spray Formulation 2

4. DISCUSSION:

4.1 Selection and Rationale for Binary Oil Blend System:

One of the critical design points was the explicit choice of a binary oil mixture consisting of only black seed oil and calendula oil and did not include additional botanical oils. This limitation was scientifically justified on multiple levels. From the perspective of mechanistic complementarity, black seed oil and calendula oil provide distinct, but complementary therapeutic effects that fully address the pathophysiology of pruritus. The thymoquinone found in black seed oil (30-48% of essential oil) dampens pro-inflammatory mediators through the inhibition of both prostaglandin and leukotriene pathways while stabilizing mast cells with antihistaminic effects. The actions of the calendula oil, containing triterpenoid saponins and flavonoids, complements the black seed oil through anti-inflammatory properties, tissue repair, emollient properties, and antimicrobial properties. This yields a rational multi-target approach with no functional redundancy. Next, the complexity and stability of formulations strongly supported a binary system. The formulation of microemulsions requires careful thermodynamic balance between phases. The inclusion of additional oils would complicate phase behaviour exponentially due to differences in solubility parameters between oils, interfacial tensions, and potential incompatibilities with phytochemicals or individual oils that would threaten spontaneous formation and stability. Our data support this approach, as all eight formulations were observed to have a degree of stability in rapid centrifugation, repeated and accelerated freeze-thaw cycles, and high-speed storage with no apparent phase separation taking place. Next, pharmaceutical standardization was greatly simplified by having two well-characterized oils, allowing for time-efficient quality control and batch-to-batch quality control by quantifying key marker compounds (e.g. thymoquinone, oleanolic acid glycosides). Lastly, the safety profile was simplified due to the presence of fewer botanical components. Both oils alone are well-absorbed and safe, any remaining oils would add increasing uncertain and unpredictable risks of allergic reactions or sensitization from a greater diversity of phytochemical componentry.

4.3 Physicochemical Characterization and Formation of Microemulsion:

The physicochemical characterization of each oil and its blends provided evidence of relevant physiochemical properties for microemulsion incorporation. The specific gravity (0.912 to 0.918), acid value (1.23 to 1.86), and peroxide value (3.2 to 5.6) confirmed the degree of freshness and quality of the oils, all fitting within acceptable pharmacopeial limits. The two blend ratios chosen BSO:CO at 60:40% and 80:20% provided a basis to study the effect of oil composition on microemulsion characteristics while also maintaining a therapeutic concentration of both active ingredients. The intermediate physicochemical parameters of the blend characterized in this study specific gravity (0.913 to 0.915) and acid value (1.6 to 1.7) indicate good miscibility of the two oils and not any chemical interaction. The choice of the surfactant’s vegetable oil ethoxylates (HCO-40, RSO-15, RSO-20) statement of significant advance toward sustainable formulations in pharmacy. The non-ionic surfactants selected for this study provided a favourable HLB value (9.7-13.1) and surface tension (40.33 to 43.25 mN/m) capable of efficient emulsification at the oil-water interface. The formulation of four separate HLB blends (11.4, 11.7, 12.4, 12.8) via calculated mixing allowed systematic exploration of the needs of the hydrophilic-lipophilic balance to create microemulsions. Furthermore, testing procedure with pseudo-ternary phase diagrams resulted in widening the microemulsion area, especially within HLB values 11.4 and 12.4, allowing justification of surfactant systems chosen.

4.4 Characterization of Microemulsions and Type of Microemulsions:

The eight formulations (F1-F8) demonstrated properties consistent with oil-in-water (O/W) microemulsions based on high electrical conductivity measures (246.4-393.4mS/m) indicating continuous aqueous phases. The droplet sizes of all eight formulations ranged from 130 to 210 nm, which align with the classical microemulsion definition (10-100nm; some sources extend microemulsions to 200nm), with all formulations of droplet sizes significantly smaller than conventional emulsions. Formulation F4 had the smallest droplet size (130nm) at HLB 11.7 with the 80:20 oil phase, possibly providing a best surfactant packing and interfacial curvature at this formulation. The nanoscale dimensions are important for dermal delivery as they significantly increase the available surface area for interaction with skin and facilitate penetration through the tortuous lipid bilayers of the stratum corneum. The pH values (6.24-6.8) of all formulations were similar to physiological skin pH (4.5-6.5) decreasing the risk of irritation with use. Viscosity measures (22.8-41.2cPs) were suitable for low viscosity and sprayable systems, with formulation F4 having the lowest viscosity (22.8cPs) providing additional support for selection as an optimal formulation. Clear to slightly translucent visual appearance of all formulations further supported the dispersed phase being on the nanoscale and the thermodynamic stability of microemulsions.

4.5 Assessment of the Stability and Robustness of the Formulations:

Through thorough stability testing, all of the developed microemulsion systems showed remarkable robustness. None of the formulations separated phases after centrifugation for 20 minutes at 3000RPM, showing evidence of strong thermodynamic stability, which sets them apart from conventional emulsions that are simply kinetically stable, and would not withstand the stress of centrifugation. Freeze-thaw cycling is one of the harshest conditions for stability testing, as changes in temperature cause changes in interfacial tension, surfactant solubility, and oil-water interaction. The formulations’ transparent appearance and lack of phase separation indicates that they retained microstructure after cycling between temperature extremes. The temperature stability assessed for 30 days at both 25°C and 45°C provided predictive information for performance over time due to how storage conditions affect microemulsion stability and the chemical and physical stability of active oils; there are minimal changes in viscosity (a maximum of 0.3 cPs), pH (a maximum decrease of 0.12 units for F1 at 45°C), and appearance. The results suggest that a surfactant film protects sensitive bioactive components like thymoquinone and carotenoids from oxidative degradation. The stability with temperature (45°C) is also important because it supports acceptable shelf life with storage in hot, humid conditions, typical in tropical and subtropical regions.

4.6 Spray Formulation Development and Functional Enhancement:

The development of spray formulations from the optimized microemulsions, which were F5 and F8 (for Formulation.1 and Formulation-2, respectively), utilized functional excipients to provide functional enhancement to the therapeutic efficacy and performance as compared to microemulsions as the basis for the general formulations. Glycerin (3% w/w) acts as a humectant by attracting and maintaining moisture in the stratum corneum to improve xerosis (dry skin) that is often reported with pruritic conditions. Panthenol (pro-vitamin B5, 0.5% w/w) has additional skin conditioning characteristics due to converting to pantothenic acid in the skin, and it supports the repair process of the epidermal barrier and has anti-inflammatory effects that would complement the actions of the active oils. The preservative system of phenoxyethanol and ethylhexyl glycerin (1% w/w) provide microbiological stability while maintaining the natural product positioning of the formulation. Disodium EDTA (0.05% w/w) acts as a chelating agent to sequester the trace metal ions that could potentially catalysed the oxidative degradation reactions. The dilution of the microemulsion to 30% w/w in the final spray formulation is a suitable compromise between therapeutic concentration of the active ingredients and the capability for the formulations to be sprayed. This dilution achieved viscosity roughly 5 cPs (as opposed to 33.6-39.5 cPs for concentrated microemulsions) to enable fine mist of the spray actuator while maintaining sufficient concentration of the active oils for therapeutic use. The clarity of the formulations and lack of phase separation following the dilution process, shows stability of the microemulsion structure.

4.7 Sensory Evaluation and Patient Acceptability:

Sensory evaluation data, while provided graphically rather than numerically, also lends important contextual information regarding patient acceptability, an important determinant of therapeutic efficacy in a real-world setting. The overall scores were high for all the areas evaluated (non-greasy feel, cooling effect, spreading ability, and overall acceptability), indicating that the microemulsion-based spray provided an aesthetic advantage compared to oil-based formulations. The non-greasy feel of the microemulsion was due to its specifically O/W microemulsion structure, whereby the oil droplets are dispersed in an aqueous continuous phase. Following application, the aqueous phase evaporated and the high scores reflected minimal oily residues on the skin surface. The cooling effect reported is most likely due to the evaporation of the aqueous phase as well as volatile components released from the essential oils that may induce sensory effects similar to menthol. The rapid spread and absorption of the microemulsion were directly related to both the nano size of the droplet and relatively low viscosity, allowing the formulation to spread rapidly on the skin surface and into the stratum corneum. Together, sensory attributes create better patient compliance and facilitate the management of chronic conditions due to the need for frequent application. The similarity between scores for Formulation-1 (F5, BSO:CO 60:40%) and Formulation-2 (F8, BSO:CO 80:20%) appears to indicate both of the oil blend ratios were acceptable, and ultimately the dosage form will be determined by formulation characteristics such as patient preference.

4.8 Mechanistic Considerations and Therapeutic Implications:

The successful establishment of black seed oil and calendula oil as stable microemulsions resolves significant mechanistic gaps in the therapy of topical pruritus using multifaceted and complementary pathways. Thymoquinone from black seed oil has been shown to reduce inflammatory mediators (prostaglandins, leukotrienes, TNF-α and interleukins), by modulating NF-κB and cyclooxygenase pathways. Furthermore, thymoquinone also occurs from mast cell membrane stabilization, preventing the release of histamine, which has been shown to be a critical mediator in the sensation of itch. The antioxidant plays a role in the efficacy by protecting the keratinocytes and fibroblasts, from reactive oxygen species during the inflammatory response. The triterpenoid saponins in calendula oil also known to improve wound healing by stimulating granulation tissue and increasing collagen also contributes to barrier function and reduced trans-epidermal water loss and xerosis skin that can be a vicious cycle perpetuating the itch-scratch defense reflex. Additionally, the fatty acids or volatile oils in calendula oil may provide anti-microbial effects to prevent secondary infections associated with pruritic dermatose. Lastly, the emollient effects contribute to improved infection of the lipid barrier function of the skin which can be impaired in pruritic dermatoses, thus reducing trans-epidermal water loss, and xerosis. The microemulsion delivery system increases the bioavailability via multiple mechanisms. First, the nanoscale dimensions of emulsions (130-210 nm) provide an enormous increased surface area for interaction with the skin, thereby increasing the thermodynamic activity and driving force for penetration. Surfactant components also have a mechanism to disrupt the lipid organisation of the stratum corneum temporarily through solubilization and fluidization of lipids, which allows the perturbation of stratum corneum lipid organisation, and creates temporally permeation pathways through the skin. The microemulsion matrix protects sensitive bioactive compounds from degradation thus preserving efficacy and potency starting from the time of manufacturing to the time of application on the skin.

5. CONCLUSION:

This study successfully formulated thermodynamically stable microemulsion-based spray formulations of black seed oil and calendula oil utilizing sustainable vegetable oil ethoxylates for the relief of pruritus. The choice of using a binary oil blend was strategic accounting for mechanistic complementarity, formulation stability, and patient safety. Eight formulations (F1-F8) possessed optimal physicochemical properties with nanoscale droplets (130-210nm), a physiological pH (6.24-6.8) and low viscosity (22.8-41.2 cPs). The stabilization studies demonstrated the formulations' robustness following centrifugation, freeze-thaw cycling, and short-term storage with few parameters remaining unchanged. The spray formulations also exhibited excellent sensory acceptability including, but not limited to, a non-greasy feel, cooling characteristics, and ease of spread. The study creates a benchmark for natural product pharmaceutical formulation through merging complementary botanical oils into a patient-oriented drug delivery system using green surfactant manufacturing technology, thereby providing promising alternatives to synthetic anti-pruritic agents.

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Received on 01.11.2025 Revised on 24.12.2025

Accepted on 29.01.2026 Published on 13.04.2026

Available online from April 15, 2026

Asian J. Pharm. Tech. 2026; 16(2):113-122.

DOI: 10.52711/2231-5713.2026.00016

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

Sr. No	Parameter	HCO 40	RSO 15	RSO 20
1	Physical appearance	Clear yellow viscous liquid	Clear yellow viscous liquid	Clear yellow viscous liquid
2	Specific Gravity	1.072	1.035	1.037
3	pH (5% solution)	6.3	6.65	6.58
4	Moisture content (%)	0.21	0.38	0.41
5	Surface tension	40.33	43.25	41.24
6	HLB value	13.1	9.7	11.7

Sr.no	Formulation	Centrifuge stability	Accelerated stability
1	F-1	No Separation	No Separation
2	F-2	No Separation	No Separation
3	F-3	No Separation	No Separation
4	F-4	No Separation	No Separation
5	F-5	No Separation	No Separation
6	F-6	No Separation	No Separation
7	F-7	No Separation	No Separation
8	F-8	No Separation	No Separation

Sr. No.	Ingredients (INCI Name)	Function	Formulation -1 (% w/w)	Formulation -2 (% w/w)
1	F-5	Microemulsion active	30	0
2	F-8	Microemulsion active	0	30
3	Disodium EDTA	Chelating agent	0.05	0.05
4	Glycerin	Humectant	3.0	3.0
5	Panthenol (Pro-vitamin B5)	Soothing and skin-conditioning agent	0.5	0.5
6	Phenoxyethanol (and) Ethyl hexyl glycerine	Preservative system	1	1
7	Citric acid	pH adjuster (to 6.2–6.8)	q.s.	q.s.
8	Purified Water	Continuous phase (solvent)	q.s. to 100	q.s. to 100

Test	Formulation	Phase separation	Visual change	Remark
Centrifugation	Formulation -1	NO	Clear, no creaming	Pass
Centrifugation	Formulation -2	NO	Clear, no creaming	Pass
Freeze–thaw cycling (3 cycles, 4 °C ↔ 45 °C, 24 h/cycle)	Formulation -1	NO	No visible change; odor unchanged	Pass
Freeze–thaw cycling (3 cycles, 4 °C ↔ 45 °C, 24 h/cycle)	Formulation -2	NO	No visible change; odor unchanged	Pass

Sr. No	Parameter	Black seed Oil and Calendula oil BSO 60 % and CO 40 %	Black seed Oil and Calendula oil BSO 80 % and CO 20 %
1	Physical appearance	Light brownish yellow	Light brownish yellow
2	Specific Gravity	0.915	0.913
3	Acid Value	1.6	1.7
4	Iodine Value	105	98
5	Peroxide Value	4.5	5.2
6	Saponification value	180	181

Blend No	HLB blend	HCO-40 (%)	RSO-15 (%)	RSO-20 (%)
1	11.4	50	50	-
2	11.7	-	-	100
3	12.4	50	-	50
4	12.8	90	10	-

Day	Formulation	Appearance/Color	pH	Viscosity (Cps)	Phase separation
0	F-1	Clear, pale yellow	6.52	5.1	None
15	F-1	Clear, pale yellow	6.47	5.0	None
30	F-1	Clear, pale yellow	6.44	5.0	None
0	F-2	Clear, pale yellow	6.56	5.3	None
15	F-2	Clear, pale yellow	6.50	5.2	None
30	F-2	Clear, pale yellow	6.49	5.2	None