The inclusion complexes of selected sunscreen agents, namely, oxybenzone (Oxy), octocrylene (Oct), and ethylhexyl-methoxycinnamate (Cin) with
Cyclodextrins (CDs) are cyclic oligosaccharides composed of glucopyranose units linked together by oxygen bridges at the 1 and 4 positions (
Complexation of various compounds with CDs leads to an enhancement in some of the characteristics of the guest molecules, such as thermalstability and photostability, bioavailability, membrane permeability, and solubility [
CDs encapsulation of a drug will affect many of the drug’s physicochemical properties without affecting its intrinsic pharmacologic properties [
CDs have been used for a variety of reasons in cosmetic preparations, such as reducing the odor in mercaptan systems, improving the stability of hair dyes, controlling volatility, and as an active ingredient in antiacne treatments [
Interaction between ethylhexyl-
Recently, there hve been growing interests in utilizing molecular mechanics (MM) and modeling to study the inclusion complexes of CDs [
In the present study, the inclusion complexation of selected sunscreen filters, oxybenzone (Oxy), octocrylene (Oct), and ethylhexyl-methoxycinnamate (Cin) (Scheme
Chemical structures of oxybenzone (Oxy), octocrylene (Oct), and ethylhexyl methoxycinnamate (Cin).
Chemical structure of
All samples were prepared by dissolving about 200 mg with different molar ratios 0 : 1, 1 : 1, and 2 : 1 of [
Dry mixing method was used in preparation of inclusion paste. The inclusion paste was formed by mixing the three sunscreen agents Oxy, Cin, and Oct and preservatives methyl paraben (MB) and propyl paraben (PP) with different amounts of
The ingredients of the sunscreen lotion with sun protection factor (SPF) 30 are shown in Table
Sunscreen lotion SPF 30 formula ingredients.
Part | Ingredient name | Weight (g) |
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A | Cin | 8 |
Oxy | 8 | |
Oct | 6 | |
MP | 0.2 | |
PP | 0.15 | |
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B | Emulgade 1000 | 8 |
Eumulgin B1 | 3 | |
Lanette 16 | 3 | |
Eutanol G | 3 | |
IPM | 1 | |
Glycerin | 5 | |
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C |
HP- |
0–10 |
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D | Water | 70 |
UV-Vis spectra were recorded with a Shimadzu single beam UV-Vis spectrophotometer (UV-2401 (PC) S). The spectra of the sunscreen agent inclusion complexes were recorded in a mixture of alcohol (methanol or ethanol) and water in 1 cm cuvette; for inclusion experiments the concentration of sunscreen agent was ~30
Differential scanning calorimetry (DSC) measurements were carried out using Shimadzu DSC-50 system equipped with a computerized data station TA-5 WS/PC and with vented aluminum pans. Thermograms of ~10 mg samples were obtained by scanning within a temperature range of 50–400°C and scanning rate of 10°C/min. An empty pan was used as a reference.
The 13C NMR spectra were recorded at 25°C using Bruker Model AC-200E spectrometer with Me4Si as an internal standard, operating at nominal 13C frequencies 63 MHz. In all measurements the solvent was DMSO-d6.
MM calculations were performed in vacuum using Hyperchem software (release 4, Hyperchem Inc., Waterloo, ON, Canada) and MM+ force field. A relative permittivity of 1.5 and conjugate gradient algorithm of 0.1 Kcal/mol Å were applied for electrostatic interaction and minimization, respectively. The
The photolysis experiments were performed by using a 150-Watt Mercury UV immersion lamp (Heraus). Photostability of all sunscreen agents was studied separately and as a mixture in lotion. The photolysis cell temperature was controlled by a flow of tap water through the photolysis jacket. The temperature was always less than 40°C. At this temperature there is no thermal degradation expected for the three sunscreen agents. The photostability of sunscreen lotion has been studied in the absence and presence of
The sunscreen assay was monitored by UV-Vis spectrophotometer. The UV-Vis spectra of the sample have been recorded before and after three hours of irradiation in time interval of one hour.
Figures
Absorption spectra of Cin (3.70 mM) in methanol/water mixture (85 : 15, v/v) as a function of
Absorption spectra of Oct (2.77 mM) in methanol/water mixture (85 : 15, v/v) as a function of
Absorption spectra of Oxy (3.17 mM) in methanol/water mixture (85 : 15, v/v) as a function of
Figure
Chemical structure of E- and Z-Cin configuration.
Oct and Oxy have given small changes in absorption upon the inclusion by
Thermal analysis methods, particularly DSC, are widely used in pharmaceutical fields, ranging from control of raw materials to stability, and preformulation studies for development of new formulation [
DSC thermograms of a
DSC thermograms of a
DSC thermograms of a
As can be noticed from Figures
Here, we have addressed the possible complexation/inclusion of the three sunscreens (Oxy, Cin, and Oct) in
13C chemical shifts of pure sunscreen agents (Oxy, Cin, and Oct), their inclusion complex with
Oxy |
Oxy |
Oxy: |
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Cin |
Cin |
Cin: |
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Oct | Oct |
Oct: |
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Table
Hypothetical structure of Oxy :
All calculations were performed using the Hyperchem software package. Importantly, the focal benefit of performing MM calculations is to provide some insights on the inclusion process that can support the experimental findings. In order to provide comprehensive computational analysis, two principal modes were considered: inclusion through the wide and narrow rims of
Reference carbon atoms used in molecular modeling approach.
The energy changes
It is worth mentioning that the inclusion complexation process is driven via a combination of forces; this includes electrostatic, van der Waals, bond angle bending, and dihedral angle bending forces. The predominant contribution to the
Table
Binding, van der Waals, and electrostatic energies with selected components at the minimum binding energy (global) for Oxy, Cin, and Oct through two rims of
Approach type | Global minimum position |
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Oxy phenyl (C*) wide rim | 0 |
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Oxy phenyl (C*) narrow rim | 1 |
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Oxy phenyl (C●) wide rim | 2 |
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Oxy phenyl (C●) narrow rim | 1 |
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Cin phenyl (C*) wide rim | 3 |
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Cin phenyl (C*) narrow rim | 1 |
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Cin hexyl (C●) wide rim | 1 |
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Cin hexyl (C●) narrow rim | 1 |
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Oct phenyl (C*) wide rim | 6 |
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Oct phenyl (C*) narrow rim | 5 |
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Oct phenyl (C●) wide rim | 6 |
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Oct phenyl (C●) narrow rim | 5 |
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Oct hexyl (C |
2 |
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Oct hexyl (C |
3 |
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Side and top views for the proposed models of the energetically favored configurations of sunscreen agents :
The MM results show that the three sunscreen agents can be included in
The complexation in water shows that the van der Waals interactions are the predominant contribution to the stabilization of the complexes formed, in which the water molecules forms a cage around the complex and no water molecule penetrates inside the
The main goal of complexation of sunscreens agents with cyclodextrins is to enhance the stability, photostability, and wettability of sunscreens agents and to reduce its skin penetration. Loftsson and Masson showed that the effect on skin penetration may be related to cyclodextrin concentration, with reduced flux generally observed at relatively high cyclodextrin concentrations [
In this study, sunscreen lotion formulation has been prepared aiming to enhance the performance of the sunscreen products. It has been noticed that the prepared lotion containing
Loss in mass of sunscreen lotion along ten days with different amounts of
The influence of
Change in absorption spectra of cream sample after different times of irradiation in the absence and presence of
Typically, the enhancement of the photostability of the molecules in the presences of cyclodextrins can be attributed to the inclusion of the guest molecule inside the CD’s cavity, either partially or entirely. Hence the photostabilization effect of the examined cyclodextin (
We believe that the results of this study demonstrate that
In the present study, we have demonstrated the ability of
MM calculations revealed that Oxy exhibited slight preference for inclusion through the wide rim over the narrow rim of the
The results of spectrophotometric study has shown that the inclusion complexation with
The authors do not have a direct financial relation with the ALFA Chemical Manufacture, Amman, Jordan (commercial identity mentioned in experiment section) that might lead to a conflict of interests for any of the authors.
Financial support by Deanship of Research at Jordan University of Science and Technology (Grant no. 30/2003) is deeply appreciated.