4. Discussion
NIR absorption spectroscopy, measurement of water content, mi- croscopy, and analysis of aspects such as rheology revealed differ- ences in the physicochemical properties of the ointments. Results of the human sensory test suggested that the feel of the ointments
18 Y. Inoue et al. / Results in Pharma Sciences 3 (2013) 15–19
Fig. 4. 2nd-Derivative near-infrared absorption spectra of triamcinolone acetonide (TA) ointments and Vaseline (PJ). (a) 2nd-derivative near-infrared absorption spectra of TA ointments and PJ observed at 4200–4400 cm −1 , (b) 2nd-derivative near-infrared absorption spectra of TA ointments and PJ observed at 4500–4800 cm −1 , and (c) 2nd-derivative near-infrared absorption spectra of TA ointments and PJ observed at 5100–5300 cm −1 .
Fig. 5. Shear stress vs. shear speed curves for TA. (a) 25 ◦C, and (b) 35 ◦C.
Fig. 6. Tan δvs. Tau for TA ointments.
differed. Results suggested a correlation between physicochemical properties and results on the human sensory test. Based on these findings, measuring physicochemical properties using various pieces of equipment may provide information correlated with feel in hu- mans. The sensory test did not indicate that TA-A and TA-B had “a good feel.”In contrast, the test indicated that TA-C had “a good feel.”This finding may indicate the effects of the presence or absence of crystal- lization, water content, and spreading. The particles in food produce gritty and unpleasant sensation with feel in humans by Lina et al have been reported [ 15 ]. Crystal is affected the usability as well ointments. Microscopy indicated potential differences in the dispersibility of the ointments.
NIR absorption spectroscopy did not reveal an absorption spec- trum specific to TA powder. Presumably, it was not detected since the TA content in preparations was 0.1%. Spectra due to olefin groups (–CH 2 ) produced at around 4200–4400 cm −1 by TA-A and TA-B were not produced by TA-C [ 13 ]. Different spectra at around 4500–4800 cm −1 were produced by TA-A, TA-B, and TA-C. Differences between oint- ments in terms of the spectra at 5100–5300 cm −1 , presumably due to hydroxyl groups (–OH), were noted [ 14 ]. These findings indicate that differences in spectra are presumably due to the differences in the types and content of additives in ointments. Differences in the absorption of –OH groups that NIR absorption spectroscopy revealed and measurements of water content indicated a higher water content for TA-C, followed almost equally by TA-A and TA-B. Based on the above results, there were differences in oil and water content and dif- ferences in ingredients in each of the creams. Accordingly, differences in the physical properties of viscosity, viscoelasticity, and spreadabil- ity may reflect differences in emulsification. The different physical properties of these creams are likely to result in a different feel when the creams are actually applied. Differences in the types and content of additives in preparations affect water and oil content. The presence of crystals and differences in dispersibility may have affected feel in the sensory test. Assessments of both the viscosity and elasticity of semisolid prepa- rations such as ointments and creams are reflected in assessments of their internal structures [ 16 ]. Determining rheology is a relatively simple and effective technique to compare the structural character- istics of creams and an efficient way to obtain information regarding their resistance to force. Assessments of structural characteristics are known to be an indicator of structural stability [ 17 ]. TA-A and TA-B had a greater area under the flow curve and underwent greater stress, suggesting that they had a stronger internal structure that was less susceptible to disruption compared to TA-C. Differences in suscepti- bility to temperature changes may be due to a different oil content and water content, i.e. the properties of bases. Oil has a lower specific heat than water, so it is readily affected by temperature. Typically, human skin temperature is considered to be about 32 ◦C [ 18 ]. When topical preparations are actually used, they are rubbed into the skin, resulting in a temperature higher than 32 ◦C due to the heat of fric- tion. In the current study, measurement was done at 35 ◦C, reflecting use of a topical preparation. Physical behavior of preparations inside their containers and on the skin may differ. TA-A and TA-B had a greater tan δthan TA-C, so they had a pro- portionately larger viscosity component. This may have led to greater cohesion. Typically, adding a solubilizing agent is known to ensure stability even at high temperatures and result in a highly viscous preparation. TA-B contained crotamiton, a solubilizing agent, and TA-B had slightly
Y. Inoue et al. / Results in Pharma Sciences 3 (2013) 15–19 19
greater viscosity than TA-A. Tajiri et al. studied the correspondence between flow curves and assessments of spreadability, and they re- ported that addition of a stabilizer hampered spreadability [ 19 ]. A preservative that TA-A contained but that TA-B did not presumably resulted in TA-B having better spreadability in the sensory test than TA-A. The feel of TA-C was due to differences in water content, pre- sumably resulting in the better spreadability of TA-C. In general, the formulation of good spreadability and without being sticky is good usability. Watery formulation is easy to extent and without the sticky. Accordingly, TA-C, watery formulation, was used feeling good. Tan δis known to be associated with the pastiness and stickiness of foods. Thus, tan δis, when talking about ointments, closely correlated with cohesiveness on a sensory test [ 20 ]. TA-A and TA-B had a greater tan δand a greater cohesiveness, suggesting a correlation with the sensory test in the current study as well. Based on the above results, differences in types and ratios of ad- ditives in TA ointments and differences in oil and water content due to those types and ratios of additives were reflected in differences in physical properties, i.e. dispersibility and viscoelasticity. Differ- ences in physical properties are surmised to cause differences in feel when ointments are actually applied. In such instances, NIR absorp- tion spectroscopy, a non-destructive method of analysis, is a useful way to identify differences in preparations [ 21 ]. Physical assessment based on NIR absorption spectra leads to information on how prepa- rations feel to patients and should provide indications of individual preferences. Thus, physical assessment of preparations can be used as a way to gather information on drugs, and such assessment can pro- vide useful information when selecting brand-name or generic drugs. A study reported that differences in the types and ratios of additives affect skin penetration [ 18 ]. Differences in physical properties are sur- mised to potentially lead to differences in clinical efficacy. Differences in physical properties may also affect skin penetration. In fact, skin penetration is attributed to physicochemical properties (lipophilic- ity and hydrophilicity) [ 22 ]. Brand-name drugs and generic drugs are considered to have equivalent quality, but their physical properties may differ. Thus, examining the correlation between physical prop- erties and skin penetration is a topic for the future.
Acknowledgements
The authors wish to thank Tarumi Toshiyasu of Japan Buchi Co., Ltd. for his helpful advice regarding NIR absorption measurements. The authors would also like to thank all of the subjects who participated in the sensory test.
References