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Quality by Design-Based Development of a Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Methylparaben, Propylparaben, Diethylamino Hydroxybenzoyl Hexyl Benzoate, and Octinoxate in Topical Pharmaceutical Formulation.

Roy C, Chakrabarty J - Sci Pharm (2014)

Bottom Line: Recovery for all the components was found to be in the range of 98-102%.The design expert with ANOVA software with the linear model was applied and a 2(4) full factorial design was employed to estimate the model coefficients and also to check the robustness of the method.Results of the two-level full factorial design, 2(4) with 20 runs including four centrepoint analysis based on the variance analysis (ANOVA), demonstrated that all four factors, as well as the interactions of resolution between DAHHB and OCT are statistically significant.

View Article: PubMed Central - PubMed

Affiliation: Analytical Research and Development, Integrated Product Development, Dr. Reddy's Laboratories Ltd., Bachupally, Hyderabad-500090, Andhra Pradesh, India. ; Department of Chemistry, National Institute of Technology, Durgapur-713209, West Bengal, India.

ABSTRACT
A stability-indicating RP-HPLC method has been developed and validated for the simultaneous determination of methylparaben (MP), propylparaben (PP), diethylamino hydroxybenzoyl hexyl benzoate (DAHHB), and octinoxate (OCT) in topical pharmaceutical formulation. The desired chromatographic separation was achieved on the Kinetex(TM) C18 (250 × 4.6 mm, 5 μm) column using gradient elution at 257 nm detection wavelength. The optimized mobile phase consisted of a buffer : acetonitrile : tetrahydrofuran (60 : 30 : 10, v/v/v) as solvent A and acetonitrile : tetrahydrofuran (70 : 30, v/v) as solvent B. The method showed linearity over the range of 0.19-148.4 μg/mL, 0.23-15.3 μg/mL, 1.97-600.5 μg/mL, and 1.85-451.5 μg/mL for MP, PP, DAHHB, and OCT, respectively. Recovery for all the components was found to be in the range of 98-102%. The stability-indicating capability of the developed method was established by analysing the forced degradation samples in which the spectral purity of MP, PP, DAHHB, and OCT, along with the separation of the degradation products from the analyte peaks, was achieved. The proposed method was successfully applied for the quantitative determination of MP, PP, DAHHB, and OCT in the lotion sample. The design expert with ANOVA software with the linear model was applied and a 2(4) full factorial design was employed to estimate the model coefficients and also to check the robustness of the method. Results of the two-level full factorial design, 2(4) with 20 runs including four centrepoint analysis based on the variance analysis (ANOVA), demonstrated that all four factors, as well as the interactions of resolution between DAHHB and OCT are statistically significant.

No MeSH data available.


Related in: MedlinePlus

Single factor interaction in the resolution between the DAHHB and OCT peaks (a) column temperature (b) mobile phase A THF composition and (c) mobile phase B THF composition
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Figure 5: Single factor interaction in the resolution between the DAHHB and OCT peaks (a) column temperature (b) mobile phase A THF composition and (c) mobile phase B THF composition

Mentions: Design Expert Software (Stat-Ease Inc., Statistics made easy, Minneapolis, MN, USA, version 7.0.0) was used for the experimental design throughout this screening process study. The full factorial design requires fewer measurements than the classical one-at-a-time experiment to give the same precision. At the same time, it detects and estimates any interaction between the factors. In order to study the simultaneous variation of the factors on the considered responses, a multivariate approach using design of experiments is recommended in robustness testing. However, if an analytical method is fast and requires the testing of a few factors (three or fewer), a good choice for robustness testing may be design expert, widely employed because of its high efficiency with respect to a fewer number of runs required in full factorial mode. In order to study the four variables at two levels, the design used in robustness testing of the resolution between the DAHHB and OCT peaks was a 24 full factorial design. ANOVA with a linear model was applied to estimate the model coefficients and also check the robustness of the method. The results of the two-level full factorial design, 24 with 20 runs, includes four centrepoints. The effects of the three factors in the resolution between the DAHHB and OCT peaks are shown in a Pareto chart (Figure 3(a)) half normal plot (Figure 3(b)). Four factors were considered: flow rate mL/min (A), column temperature (B), tetrahydrofuran composition% in mobile phase A (C), and tetrahydrofuran composition% in mobile phase B (D). The factors and level considered (response) for the studies are shown in Table 1. Standards of DAHHB and OCT were prepared in assay concentrations. The critical resolution between the DAHHB and OCT peaks was studied as a response. No power transformation for the significance of the model was required as shown in the Box-Cox plot (Figure 4). The effect plot of the different factors revealed a decrease in the resolution between the DAHHB and OCT peak by an increase in factor B (column temperature) (Figure 5(a)), while an increase in the resolution between the DAHHB and OCT peak was observed with an increase in factor C (THF composition in mobile phase A) (Figure 5(b)), and factor D (THF composition in mobile phase B) (Figure 5(c)).


Quality by Design-Based Development of a Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Methylparaben, Propylparaben, Diethylamino Hydroxybenzoyl Hexyl Benzoate, and Octinoxate in Topical Pharmaceutical Formulation.

Roy C, Chakrabarty J - Sci Pharm (2014)

Single factor interaction in the resolution between the DAHHB and OCT peaks (a) column temperature (b) mobile phase A THF composition and (c) mobile phase B THF composition
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4318166&req=5

Figure 5: Single factor interaction in the resolution between the DAHHB and OCT peaks (a) column temperature (b) mobile phase A THF composition and (c) mobile phase B THF composition
Mentions: Design Expert Software (Stat-Ease Inc., Statistics made easy, Minneapolis, MN, USA, version 7.0.0) was used for the experimental design throughout this screening process study. The full factorial design requires fewer measurements than the classical one-at-a-time experiment to give the same precision. At the same time, it detects and estimates any interaction between the factors. In order to study the simultaneous variation of the factors on the considered responses, a multivariate approach using design of experiments is recommended in robustness testing. However, if an analytical method is fast and requires the testing of a few factors (three or fewer), a good choice for robustness testing may be design expert, widely employed because of its high efficiency with respect to a fewer number of runs required in full factorial mode. In order to study the four variables at two levels, the design used in robustness testing of the resolution between the DAHHB and OCT peaks was a 24 full factorial design. ANOVA with a linear model was applied to estimate the model coefficients and also check the robustness of the method. The results of the two-level full factorial design, 24 with 20 runs, includes four centrepoints. The effects of the three factors in the resolution between the DAHHB and OCT peaks are shown in a Pareto chart (Figure 3(a)) half normal plot (Figure 3(b)). Four factors were considered: flow rate mL/min (A), column temperature (B), tetrahydrofuran composition% in mobile phase A (C), and tetrahydrofuran composition% in mobile phase B (D). The factors and level considered (response) for the studies are shown in Table 1. Standards of DAHHB and OCT were prepared in assay concentrations. The critical resolution between the DAHHB and OCT peaks was studied as a response. No power transformation for the significance of the model was required as shown in the Box-Cox plot (Figure 4). The effect plot of the different factors revealed a decrease in the resolution between the DAHHB and OCT peak by an increase in factor B (column temperature) (Figure 5(a)), while an increase in the resolution between the DAHHB and OCT peak was observed with an increase in factor C (THF composition in mobile phase A) (Figure 5(b)), and factor D (THF composition in mobile phase B) (Figure 5(c)).

Bottom Line: Recovery for all the components was found to be in the range of 98-102%.The design expert with ANOVA software with the linear model was applied and a 2(4) full factorial design was employed to estimate the model coefficients and also to check the robustness of the method.Results of the two-level full factorial design, 2(4) with 20 runs including four centrepoint analysis based on the variance analysis (ANOVA), demonstrated that all four factors, as well as the interactions of resolution between DAHHB and OCT are statistically significant.

View Article: PubMed Central - PubMed

Affiliation: Analytical Research and Development, Integrated Product Development, Dr. Reddy's Laboratories Ltd., Bachupally, Hyderabad-500090, Andhra Pradesh, India. ; Department of Chemistry, National Institute of Technology, Durgapur-713209, West Bengal, India.

ABSTRACT
A stability-indicating RP-HPLC method has been developed and validated for the simultaneous determination of methylparaben (MP), propylparaben (PP), diethylamino hydroxybenzoyl hexyl benzoate (DAHHB), and octinoxate (OCT) in topical pharmaceutical formulation. The desired chromatographic separation was achieved on the Kinetex(TM) C18 (250 × 4.6 mm, 5 μm) column using gradient elution at 257 nm detection wavelength. The optimized mobile phase consisted of a buffer : acetonitrile : tetrahydrofuran (60 : 30 : 10, v/v/v) as solvent A and acetonitrile : tetrahydrofuran (70 : 30, v/v) as solvent B. The method showed linearity over the range of 0.19-148.4 μg/mL, 0.23-15.3 μg/mL, 1.97-600.5 μg/mL, and 1.85-451.5 μg/mL for MP, PP, DAHHB, and OCT, respectively. Recovery for all the components was found to be in the range of 98-102%. The stability-indicating capability of the developed method was established by analysing the forced degradation samples in which the spectral purity of MP, PP, DAHHB, and OCT, along with the separation of the degradation products from the analyte peaks, was achieved. The proposed method was successfully applied for the quantitative determination of MP, PP, DAHHB, and OCT in the lotion sample. The design expert with ANOVA software with the linear model was applied and a 2(4) full factorial design was employed to estimate the model coefficients and also to check the robustness of the method. Results of the two-level full factorial design, 2(4) with 20 runs including four centrepoint analysis based on the variance analysis (ANOVA), demonstrated that all four factors, as well as the interactions of resolution between DAHHB and OCT are statistically significant.

No MeSH data available.


Related in: MedlinePlus