70 BODY CARE
cage, between hourly intervals. The outcomes provide the CPT (Complete Protection Time) and the PE (Protection Efficiency) score. The CPT score (Table 1) measures the
time between product application and the occurrence of the first confirmed probe or bite on the treated arm. The PE score (Table 2) records the number
of mosquitos probing or biting the treated arm compared simultaneously with the untreated (control) arm, during a 60-second exposure, between hourly intervals throughout the test, for up to eight hours or until the product no longer provides 50% protection – at which point the test ends.
No. mosquitoes probing untreated arm - No. mosquitoes probing treated arm
Total No. mosquitoes probing untreated arm
x100= Protection Efficiency Importantly, the repellent effect has been
shown to be reproducible across all of the major sub-species of mosquito that are vectors for disease. Supportive data generated by external laboratories confirms the efficacy against Anopheles (malaria), Culex (West Nile virus) and Aedes (dengue, yellow fever, Zika virus, chikungunya). Looking beyond the public health threat posed by mosquitoes, PMD also displays a broad spectrum repellent effect against other biting insects and nuisance species such as ticks, mites, bed bugs, head lice and wasps.
Formulating water-based product from a PMDRBO derived from Eucalyptus citriodora feedstock The main challenge in formulating a water- based product from a PMDRBO derived from Eucalyptus citriodora feedstock, has been the crystalline nature of the product. At room temperature the product is semi solid - typically a dual phase mixture of a crystalline solid (PMD) and a variable liquid fraction, which can be anything between 30-100% of the total mixture. The crystalline phase can be easily
reconstituted by warming (typically at temperature > 50 C) to give a homogenous liquid that can then (with care) be taken up
100 90 80 70 60 50 40 30 20 10 0
15% Citrepel 75
TABLE 1: MEDIAN COMPLETE PROTECTION TIMES (CPT) AND LOWER AND UPPER 95% CONFIDENCE INTERVALS (CI) FOR FOUR DOSES OF PMD AGAINST Ae. aegyptiMOSQUITOES
Product
5% Citrepel 75 10% Citrepel 75 15% Citrepel 75 20% Citrepel 75
Median CPT (upper and lower CI) (hh:mm)
2:01 (1:55-2:07) 2:05 (1:06-3:03) 3:58 (3:19-4:36)
5:00 (00:09-9:50)
in the solvating medium (typically ethanol, mixtures of ethanol and water or other polar solvents e.g. dipropylene glycol, isopropyl myristate, benzyl acetate). These PMD solutions can then be delivered through LPG aerosol or pump spray, using suitable solvent resistant packaging media and closures (typically aluminium). Producing a stable, water-based product without solvents, that can also be cold processed, is less straightforward. Having first homogenised the active, the emulsification step produces a supersaturated PMDRBO (oil) phase that will inevitably begin to recrystalise at ambient temperature and below. Polar solvents, like those previously
mentioned, are the most suitable for preventing that re-crystallisation by keeping the PMD component of the oil solubilised. However, the polarity of these solvents imparts a degree of water miscibility and solvated PMD can be translocated across the weak phase boundary, leading to seeding and crystal ripening within the aqueous phase. The unwanted consequence of this being a blockage of the spray nozzle and non-uniform PMD concentration through the body of the formulation. This effect can be countered through the
modification of the solvating medium with less polar, hydrocarbon solvents, creating a phase boundary with higher surface potential. For effective long-term storage stability, this boundary has then to be stabilised, typically with higher molecular weight, polymeric materials such as PVOH/PVA copolymer, used in conjunction with the primary emulsifying surfactant and a water soluble thickener. The emulsion concentrate (EW) so
produced comprises a carefully balanced mixture of active, solvents, surfactant(s), emulsion stabiliser(s), thickener and water.
50% PE ■ Aedes aegypti ■ 0.0 1.0 2.0 3.0 4.0 5.0 6.0 Hours
Figure 2: Combined protective efficacy of 15% Citrepel 75 against Ae. aegypti mosquitoes
PERSONAL CARE October 2024 7.0 8.0 9.0 10.0 11.0 12.0
100 90 80 70 60 50 40 30 20 10 0
TABLE 2: MEDIAN TIME TO 50% PROTECTIVE EFFICACY AND LOWER AND UPPER 95% CONFIDENCE INTERVALS (CI) FOR FOUR DOSES OF PMD AGAINST Ae. aegyptiMOSQUITOES
Product
5% Citrepel 75 10% Citrepel 75 15% Citrepel 75 20% Citrepel 75
Median time to 50% PE
(upper and lower CI) (hh:mm) 2:01 (1:55-2:07)
2:05 (1:06-3:03) 3:58 (3:19-4:36)
5:00 (00:09-9:50) Consequently, the space remaining within
the formulation for the active ingredient itself is necessarily reduced - with implications for the overall efficacy of the formulation, given the proportional relationship between active ingredient loading (% PMD content) and CP and PE scores (Figures 2 and 3). The second generation, Cosmos Certified, PMDRBO based on refined Java Citronella oil (Fractionated Cymbopogon winterianus) presents opportunities for a much simpler, cold process alternative, with lower material cost and no requirement for co-solvents. Citrepel 75 in its pure form, is itself a
homogenous liquid at ambient temperature with low viscosity, very low odour and high PMD content (typically 75 % w/w). The liquid PMDRBO can be premixed, without warming, with emulsifier and water soluble gum and then added directly to water at room temperature under normal agitation, with mixing time between 15 and 20 minutes. The emulsified oil phase is stable, not prone
to crystallisation and a variety of formulation types are possible, with PMD content up to 35 % and above, to give continuous protection in the most extreme conditions. This 20% Citrepel 75 emulsion has been
evaluated in a three-year GLP stability study (for submission within the BPR dossier) and was found to physically and chemically stable throughout the three-year period. The emulsion is also self-preserving due
to the inherent biocidal properties of PMD. Independent challenge test results on high water formulations (5% C75 emulsion) indicate that the emulsion does not require preservatives. Details of challenge test results are available on request.
The homogenous nature of the active
material with low propensity for crystallisation of PMD, also lends itself to various encapsulation techniques that are being used to extend the
50% PE ■ Aedes aegypti ■ 20% Citrepel 75
0.0
1.0
2.0
3.0
4.0
5.0
6.0 Hours
Figure 3: Combined protective efficacy of 20% Citrepel 75 against Ae. aegypti mosquitoes
www.personalcaremagazine.com
7.0
8.0
9.0
10.0
11.0
12.0
Protective Efficacy (%)
Protective Efficacy (%)
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