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Development of hair serum from local coffee by-product

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Abstract and Figures

Nowadays, Thai consumers are more alert and caring about their hair health. As a result, products that care and promote hair and scalp are in high demand. One of the most interesting products is the hair care line. One of the important substances that help in reducing hair loss and promoting hair regrowth is coffee extract. This research focuses on value creation of coffee products from the northern Thailand into a cosmeceutical product. Variety of coffee by-product are studied in terms of Caffeine content and antioxidant activity, which benefit the hair growth and scalp care function. In addition, product development technique has been implemented to develop the hair serum prototype that comply with customer’s requirement. The results show that the active ingredient can be extracted from a variety part of coffee by- product. The coffee bean extraction yields the highest amount of Caffeine, while the red coffee fruit extraction yields the highest amount of antioxidant activity. However, when compare in terms of performance/cost of material, the extraction of fall grade cherry coffee is the most cost effective source for both active ingredients for this serum development. In the meantime, the market demand was collected based on 252 sample size using online questionnaires. The results show that the sample group gave importance to the factor of no irritation to the scalp as the first concern, while the safety issue as the second and the properties of the product ranked the third on customer’s needs. Then the prototype was developed and verified in terms of active ingredient concentration and product stability. Furthermore, product was validated in terms of hair growth and skin irritation. Finally, the prototype was analyzed with 3 focus groups: (1) hair loss prevention group (2) hair loss solution group and (3) beauty service provider/ product supplier. According to these focus group evaluation, it shows that all three test participants were satisfied with prototype’s sensory. Some issues that could be improved are viscosity and stickiness. Additionally, marketing mix was evaluated on these group to estimate potential product-package design, selling price and place, as well as the promotion technique.
Content may be subject to copyright.
AIP Conference Proceedings 2397, 020003 (2021); https://doi.org/10.1063/5.0063780 2397, 020003
© 2021 Author(s).
Development of hair serum from local coffee
by-product
Cite as: AIP Conference Proceedings 2397, 020003 (2021); https://doi.org/10.1063/5.0063780
Published Online: 15 September 2021
Wassanai Wattanutchariya, Phisit Seesuriyachan, Bussaba Arree, Araya Raiwa, Kochakon Moonsub, Jaturapit
Phongsupa, et al.
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Development of Hair Serum from Local Coffee By-Product
Wassanai Wattanutchariya1,a), Phisit Seesuriyachan2,b), Bussaba Arree3,c), Araya Raiwa4,d),
Kochakon Moonsub1,e), Jaturapit Phongsupa1,f)
1Advanced Manufacturing and Management Technology Research Center (AM2Tech), Department of Industrial
Engineering, Faculty of Engineering, Chiang Mai University, Chiang Mai 50200, Thailand
2Faculty of Agro-Industry, Chiang Mai University, Chiang Mai 50200, Thailand
3Faculty of Accountancy, Economics and Finance, Payap University, Chiang Mai, Thailand 50000
4Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
a)Corresponding author: wassanai@eng.cmu.ac.th
b)phisit.seesuriyachan@gmail.com, c) bussaba_a@payap.ac.th, d) araya.raiwa@gmail.com,
e) kochakon_moo@cmu.ac.th, f) jaturapit_phongsupa@cmu.ac.th
Abstract. Nowadays, Thai consumers are more alert and caring about their hair health. As a result, products that care and
promote hair and scalp are in high demand. One of the most interesting products is the hair care line. One of the important
substances that help in reducing hair loss and promoting hair regrowth is coffee extract. This research focuses on value
creation of coffee products from the northern Thailand into a cosmeceutical product. Variety of coffee by-product are
studied in terms of Caffeine content and antioxidant activity, which benefit the hair growth and scalp care function. In
addition, product development technique has been implemented to develop the hair serum prototype that comply with
customers requirement. The results show that the active ingredient can be extracted from a variety part of coffee by-
product. The coffee bean extraction yields the highest amount of Caffeine, while the red coffee fruit extraction yields the
highest amount of antioxidant activity. However, when compare in terms of performance/cost of material, the extraction
of fall grade cherry coffee is the most cost effective source for both active ingredients for this serum development. In the
meantime, the market demand was collected based on 252 sample size using online questionnaires. The results show that
the sample group gave importance to the factor of no irritation to the scalp as the first concern, while the safety issue as the
second and the properties of the product ranked the third on customers needs. Then the prototype was developed and
verified in terms of active ingredient concentration and product stability. Furthermore, product was validated in terms of
hair growth and skin irritation. Finally, the prototype was analyzed with 3 focus groups: (1) hair loss prevention group (2)
hair loss solution group and (3) beauty service provider/ product supplier. According to these focus group evaluation, it
shows that all three test participants were satisfied with prototypes sensory. Some issues that could be improved are
viscosity and stickiness. Additionally, marketing mix was evaluated on these group to estimate potential product-package
design, selling price and place, as well as the promotion technique.
KeywordsCoffee Extract, Hair Serum, Quality Function Deployment, Product Development
INTRODUCTION
Coffee is one of the most popular beverages in the world with a constant increase in consumption. Arabica coffee
is one of the coffee type that has been cultivated in many regions in the northern part of Thailand. In the process of
coffee production, a large number of by-product are created such as husks, hulls, defective beans, and coffee silverskin.
These coffee by-products could be used not only as a fertilizer, but also a source of many bioactive compounds that
can be extracted and used for food, cosmetic and pharmaceutical purposes [1]. In the meantime, the cosmetic industry
is one industry that is growing and expanding continuously. Cosmeceuticals are another option for people who care
for themselves. Cosmeceuticals combines the properties of cosmetics and drugs together, which are a new product
category in cosmetic industry [2]. According to statistics, the market for cosmeceutical in Thailand has a market value
The 7th International Conference on Engineering, Applied Sciences and Technology
AIP Conf. Proc. 2397, 020003-1–020003-7; https://doi.org/10.1063/5.0063780
Published by AIP Publishing. 978-0-7354-4124-8/$30.00
020003-1
of up to 2,000 million baht per year and a high growth rate of 30 percent per year, making the cosmeceutical product
sector grow rapidly. Recently, anti-hair loss activity caffeine has received a lot of attention in the manufacture of
cosmetic products. Which not only improves the scalp but also appears to help maintain hair condition from 5Į-
reductase inhibition activity. This enzyme can convert testosterone to active dihydrotestosterone (DHT) that
contributes to baldness, thus renewing the hair growth phase [3]. According to a recent study, it showed that caffeine
concentrations from 0.001 to 0.005% resulted in the in vitro growth of hair follicle cells due to caffeine
phosphodiesterase. It inhibits the increase in intracellular cAMP and stimulates cellular metabolism. In addition,
caffeine reduces the tension in the smooth muscles in the hair follicles, resulting in better nutrient transmission.
Caffeine also stimulates the microcirculation of the capillaries to nourish the hair. Furthermore, some researchers
showed that exposure to caffeine-induced hair-shampoos has been shown to decrease the risk of hair loss [4-5].
Another study also showed that caffeine can penetrate deep into the pores and it remains for up to 48 hours even after
washing the hair when it is expose to human skin for 2 minutes [6]. With these literatures, coffee by-product with high
caffeine content could be further develop into an anti-hair loss serum. This study implemented product development
techniques to develop hair serum product from local material to meet market needs. Cost effective coffee by-product
will be analyzed and develop into hair serum based on the user expectation. Quality function deployment or QFD,
which is a tool in product development approach [7-9], is implemented to convert consumer demand into technical
features, and prioritize each feature upon the prototype development and sensory evaluation.
MATERIAL AND METHODS
The research started with data collection in two perspectives: local material properties and product customer
expectation. The raw material investigation focused on laboratory research along with cost data collection from local
farmer to compare its cost-effectiveness. Meanwhile, the customer-side data collection was based on interviews and
questionnaires. Both information was then used to develop hair care products through the QFD technique. The details
of various research activities are as follows:
Characterizing of Active Ingredients and Cost
In order to select proper raw materials for cost-effective production, various forms of coffee by-products were
studied for their chemical properties consistent with the development of hair care products. It consists of various parts
of coffee, i.e., all red coffee fruit (grade A), fall-grade coffee fruit (mixed color), coffee beans, and only the cherry
coffee peel. The properties that is under investigation were caffeine concentration which characterized by HPLC (High
Performance Liquid Chromatograph), and antioxidant activity measured by DPPH radical scavenging assay.
Potential Customers Data Collection
The data collection was carried out by surveying the needs of target customers with in-depth interviews of at least
20 persons. Then, the customers responses were interpreted into closed end questions using affinity diagram. Following
by the distribution of online questionnaires targeting at consumer related to hair care product. The information obtained
is the issue of evaluating the product characteristics that customers need and expect for the developing product.
QFD Matrix Development
HOQ is used to assess the consumer's needs and to further improve the product [10]. HOQ allows the development
of a hair serum to meet the needs of the consumer by correlating the consumer's needs with the technical requirements
of the consumer. The product Data from online questionnaires are used in the HOQ format, an analysis of the general
relationship of consumer demand to the technical characteristics of the product. Moreover, target specification and
priority of importance rating for technical characteristic were supported the development of the product prototype [11].
Prototype Development and Sensory Evaluation
The research team has developed a product prototype based on the results of QFD as well as other demand data
from the interview. The formulation of anti-hair loss products was carried out according to customer needs and literature
review. Sensory evaluation of the prototype was analyzed to access the level of customer satisfaction and solicit the
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recommendation for product refinement prior to commercialization. Three focus groups were recruited consisting of
hair loss prevention group, hair loss solution group, and beauty service provider/product supplier.
RESULTS AND DISCUSSIONS
Characterizing of Active Ingredients and Cost
The study focused on the properties of the active ingredient that extracted from local coffee to evaluate cost-
effective raw material for the production of the hair serum. The raw materials are separated into 4 types as follows:
(1)red coffee fruit (2) fall grade coffee (3) coffee beans (4) coffee peel, which has different prices from farmers in
Doi Chang community. The characterizations of these raw materials were performed in terms of caffeine content and
antioxidant activity.
Caffeine content of the coffee extractions were characterized by HPLC, as shown in Table 1. As can be seen, the
extraction from coffee bean yielded the highest amount of caffeine content than other types of coffee by-product.
Antioxidant activity of the coffee extractions were characterized by DPPH radical scavenging assay. The result shows
that the extraction from red coffee fruit yielded the highest amount of antioxidant activity than other types of coffee
by-product, as shown in Table 2. This table also shows that all by-product parts had the ability to inhibit the enzyme
DPPH at 50% (IC50) at a concentration of more than 100 mg ml.
TABLE 1. Caffeine content of coffee by-product extraction
Extracted part
Caffeine
(mg/g extract)
Red coffee fruit
4.66±0.01
Fall-grade coffee fruit
Coffee beans
Coffee peel
4.14±0.36
7.24±0.15
2.23±0.24
TABLE 2. Antioxidant activity of coffee by-product extraction
Extracted part
DPPH radical scavenging assay
IC
50
(mg/ml)
Antioxidant activity
(mg trolox equivalent /g extracts)
Red coffee fruit
>100
4.38±0.02
Fall-grade coffee fruit
Coffee beans
Coffee peel
>100
>100
>100
3.92±0.12
4.33±0.08
0.80±0.06
Cost estimation of coffee extract was used to assess the market potential for prototype coffee production. This
includes the cost effectiveness of raw materials, which each type of raw material cost comes from the data collected
from the Doi Chang community coffee farmers. According to market price, the cost for red coffee fruit, fall-grade
coffee fruit, coffee bean, and coffee peel are 26 baht/kg, 19 baht/kg, 250 baht/kg, and 6 baht/kg, respectively.
Therefore, the cost effectiveness in terms of ratio between active ingredient to raw materials cost can be calculated.
The calculation shows that the most cost-effective caffeine content is the coffee peel, while the most cost-effective
antioxidant activity is fall-grade coffee fruit. This information was considered as an input for QFD evaluation and
development of an appropriate product prototype.
Potential Customers Data Collection
It is necessary to know the user behavior and customer expectation in order to understand the purpose of product
design and development. First, an in-depth interview of 20 persons were carried out. The participants are service
providers in the beauty salon, including marketing experts, professional nurses, business people and entrepreneurs
dealing with beauty services. Responses from the interview were then interpreted and categorized by affinity diagram
as shown in Fig.1. Factors effecting the customer requirement were transformed into questionnaire. Information about
consumer behavior and expectation was collected within the same questionnaire.
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FIGURE 1. Analysis of user requirement with Affinity Diagram
According to the 252 respondents, 57.14% are female and 39.29% are male. The majority age range is between
20-35 yr., followed by 36-50 yr. and over 50 yr. Government officials, enterprise employees, and student are the top
three occupations of the respondents. Most respondent can accept the product price (100 ml. bottle) at 300 baht.
Additionally, benchmarking product in the same category of hair care product are Schwarzkopf professional and
Bergamot hair tonic. Furthermore, factors influencing their decision to purchase hair loss products other than the
benefit of hair loss prevention, are allergy free, no itchy scalp, safety/standard compliance, as well as benefit for hair
and scalp care.
QFD Matrix Development
The results obtained from the survey, were input into the left side of QFD matrix, as shown in Fig. 2. Then the
technical requirements were illustrated and evaluated in terms of their relationship to the customer requirement. Three
level of interrelationship between customer needs and technical requirement are determined by research teams to
transform and prioritize product characteristics to be developed to the prototype. Moreover, improvement direction
and the target value for each technical requirement are stated in this matrix to inform the R&D team during prototype
development. According to the importance rating of product characteristics, the most important issue is the coffee
extract content which can enrich hair serum, followed by the cost and safety issues of the product.
Prototype Development and Sensory Evaluation
According to the result of QFD and prior data collection, the main concerns of target customer are related to the
capability of product to prevent hair loss as well as to provide benefit to new hair growth. Our pharmaceutical
researcher has developed the new formulation of hair serum based on coffee by-product complying with the customer
requirement. Furthermore, safety issues relating to technical requirement IMP were under consideration by performing
the irritation and cytotoxicity test during the prototype development of cosmeceutical products, hair and scalp care.
The prototype of this research is illustrated in Fig. 3, which contains active ingredient from coffee extract resulting in
slightly brown color and coffee aroma. Additionally, the chosen package allows the serum to be sprayed as a fine mist
direct to users scalp without greasy feeling.
Based on the focus group evaluation, results show that the product prototype had a good sensory acceptance. The
issues that should be improved are viscosity and stickiness. Test participants wanted a product with the right viscosity
but not sticky. It was found that at a production cost of approximately 60 baht, it is possible to penetrate the target
consumer with the markup price of 300-500 baht per package. Figure 4 illustrates the radar chart of sensory evaluation
among 3 type of hair serum: revised version of our prototype (A), commercial product B and C. As can be seen, our
current product prototype has the score higher than other counter-brand hair serums. The results of this research will
lead to the registration of products available for market in the future.
Marketing
Physical
Safety
Reduce hair loss
Smell
Standard certified
Packaging
Portable bottle
Does not cause
allergies or itchy
scalp
Non-sticky /
absorbs quickly
Extracted from
natural ingredients
The bottle is easy to
Clinical properties
Stimulate
regeneration
of hair
Price
Nourishes the scalp
Strong hair
Black hair
Color
Packaging contains
product information.
020003-4
Correlations
Positive
+
Negative
-
No Correlation
Relationships
Symbol
Meaning
Score
Ɣ
Strong
9
ż
Moderate
3
Weak
1
Direction of Improvement
Maximize
Ÿ
Target
Minimize
ź
FIGURE 2. QFD matrix of Hair serum from local coffee by-product
Ÿ
ᶻ
Ÿ
ᶻ
ᶻ
ᶻ
ᶻ
ᶻ
ᶻ
ᶻ
ź
ᶻ
ź
Physical
attributes
Safety
Chemical
properties
Packaging
Marketing
Demand factors that affect
product attributes
IMP
Smell
Color
Stickiness
Ratio of Natural Ingredient
Irritation test
Biocompatibility tests
Safety standards
Coffee extract
content
Active Ingredient A
Active Ingredient B
Package selection
Packaging Detail
Product cost
Physical
abilities
Smell
3.98
Ɣ
ż
Color
2.76
Ɣ
ż
ż
ż
ż
Not sticky
4.03
Ɣ
Safety
Developed from natural
ingredients
4.10
ż
ż
ż
Ɣ
Ɣ
Ɣ
Ɣ
Ɣ
ż
ż
ż
Do not cause allergies
or itchy scalp
4.65
ż
Ɣ
Ɣ
Ɣ
Ɣ
ż
ż
ż
Have standard/safety
certification
4.58
ż
Ɣ
Ɣ
Ɣ
ż
ż
ż
ż
Clinical
properties
Function for hair and
scalp care
4.49
ż
ż
ż
ż
ż
Ɣ
Ɣ
Ɣ
Ɣ
Packaging
The container is
convenient to use
3.67
Ɣ
ż
Clear information on
external package
4.07
Ɣ
ż
Marketing
Price
4.22
Ɣ
Ɣ
Target Value
Passed the sensory test
Passed the sensory test
Passed the sensory test
> 50%
Tested for irritation on
volunteers
Passed the biological
compatibility test
Passed the FDA standard
Consistent with the
developed formula
50ml spray type package
Clear information
presented
<100 baht per bottle
Total score
Relative Technical Requirement
101
86
130
198
314
314
302
329
191
191
158
77
319
2,711
Absolute Technical Requirement (IMP)
4%
3%
5%
7
%
12%
12
%
11
%
12%
7%
7%
6%
3%
12%
100%
+
+
-
+
+
+
+
+
+
-
-
-
020003-5
0.0
1.0
2.0
3.0
4.0
5.0
ÿĊ
Öúĉęî
ÙüćöĀîČé
ÙüćöđĀîĂąĀîą
ÖćøĒñŠÖøąÝć÷
ïîĀîĆÜýĊøþą
ÙüćöóċÜóĂĔÝ
ēé÷øüö
ñúĉêõĆèæŤ A
ñúĉêõĆèæŤ B
ñúĉêõĆèæŤ C
FIGURE 3. Prototype of hair serum from local coffee by-product
FIGURE 4. Sensory evaluation with model A and comparator B and C
CONCLUSION
This research focused on developing high-value added product based on local material which is coffee by-product
from Doi Chang, Chiang Rai, Thailand. First of all, different types of by-product were analyzed in terms of active
ingredient content as well as the cost per unit. The result show that the most cost-effective caffeine content is the
coffee peel, while the most cost-effective antioxidant activity is fall-grade coffee fruit. Then, QFD technique has been
employed to access customer requirement and transform to product characteristics. Depth interview was performed to
collect qualitative information, then develop into an online questionnaire. The response from questionnaire shows
that hair care customer pay attention to both products safety issue and pharmaceutical function. With respect to QFD
matrix, the product specifications were evaluated and prioritized. According to the importance rating of product
characteristics, the most important issue is the coffee extract content, followed by the cost and safety standard of the
product. After QFD implementation, the prototype product was developed and tested in the laboratory to comply with
safety standard as well as to confirm the hair and scalp care benefit. Finally, the sensory evaluation was performed on
3 groups of target customers. The result shows that all groups have rate the prototype product with a good acceptance
score. Few issues have been raised such as viscosity and stickiness of the prototype which then been revised in the
second version of the prototype. In addition, when comparing sensory results with two peer commercial products, it
shows that our recent prototype has a higher score in every sensory attribute. Further study on marketing and up-scale
production will be performed prior to the commercialization of this hair serum product in the near future.
Color
Smell
Overall
Satisfaction
Viscosity
Stickiness
Spreadability
Product A
Product B
Product C
020003-6
ACKNOWLEDGMENTS
The authors would like to acknowledge the support from Thailand Science Research and Innovation Fund under
grant number RDG62T0050Potential Enhancement for Coffee Entrepreneur by High Value-added Product
Development and Holistic Management in Doi Chang Community, and Chiang Mai University.
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3. T. W. Fischer, U. C. Hipler, and P. Elsner. “Effect of caffeine and testosterone on the proliferation of human hair
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Sterry, and Jürgen Lademann.. “The role of hair follicles in the percutaneous absorption of caffeine, British
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7. K. T. Ulrich and S. D. Eppinger, Product Design and Development, 7th Edition, McGraw-Hill, New York, (2020)
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In the present study, the ability of a shampoo formulation containing caffeine as well as the fluorescent dye fluorescein to penetrate into hair follicles was investigated by in vivo laser scanning microscopy. A contact time of two minutes between the shampoo and the skin surface was sufficient for the formulation to penetrate deeply into the hair follicles and to remain there for up to 48 hours, even after washing. As hair follicles are surrounded by a close network of capillaries, dendritic cells and stem cells, they represent an important target for drug delivery. The results of the present study demonstrated that in vivo laser scanning microscopy is an efficient tool for the investigation of the dermatopharmacokinetics of topically applied molecules and their penetration pathways, as the method yields space- and timeresolved measurements. (© 2007 by Astro Ltd., Published exclusively by WILEY-VCH Verlag GmbH & Co. KGaA)
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In previous in vitro investigations, it was demonstrated that caffeine is able to stimulate the hair growth. Therefore, a penetration of caffeine into the hair follicle is necessary. In the present study, in vivo laser scanning microscopy (LSM) was used to investigate the penetration and storage of a caffeine containing shampoo into the hair follicles. It was shown that a 2-min contact time of the shampoo with the skin was enough to accumulate significant parts of the shampoo in the hair follicles. A penetration of the shampoo up to a depth of approx. 200 μm could be detected, which represents the detection limit of the LSM. At this depth, the close network of the blood capillaries surrounding the hair follicles commences. Even after 24 h, the substance was still detectable in the hair follicles. This demonstrates the long-term reservoir function of the hair follicles for topically applied substances such as caffeine.
Article
Androgenetic alopecia (AGA) is a common problem in men of all ages, affecting approximately 50% at 50 years of age. The underlying cause is an androgen-dependent miniaturization of genetically predetermined hair follicles. Here, the hair organ culture model was used to investigate the effects of testosterone and caffeine; the latter being a promising candidate for hair growth stimulation. Hair follicles from 14 biopsies, taken from the vertex areas from male AGA patients, were cultivated for 120-192 h in vitro with normal William's E medium (control) or William's E medium containing different concentrations of testosterone and/or caffeine. Hair shaft elongation was measured daily and at the end of cultivation, cryosections of follicles were stained with Ki-67 to evaluate the degree and localization of keratinocyte proliferation. Significant growth suppression was found in hair follicles treated with 5 microg/ml testosterone. This was counteracted by caffeine in concentrations of 0.001% and 0.005%. Moreover, caffeine alone led to a significant stimulation of hair follicle growth. These results were confirmed immunohistochemically by Ki-67 staining. Androgen-dependent growth inhibition of ex vivo hair follicles from patients suffering from AGA was present in the human hair organ culture model, a constellation which may serve for future studies to screen new substances against androgen-dependent hair loss. Caffeine was identified as a stimulator of human hair growth in vitro; a fact which may have important clinical impact in the management of AGA.
Article
What is already known about this subject: * In recent years, it has been suggested that hair follicles represent important shunt routes into the skin for drugs and chemicals [1-3]. * In vitro studies have shown the importance of skin appendages for skin penetration by hydrophilic compounds [4]. Investigation of follicular penetration in vivo has been difficult due to the absence of appropriate analytical methods or suitable animal model systems. * Recently, a new method was described that quantifies follicular penetration in vivo by using selective closure of hair follicles [5]. * Caffeine is frequently used in skin penetration experiments as a model for highly water-soluble compounds. Occlusion [6] and skin thickness [7] seem to have little influence on the penetration of caffeine. However, percutaneous absorption rates for caffeine exhibit regional skin differences in humans in vivo[1]. What this study adds: * The results of the present study demonstrate that a fast drug delivery of caffeine occurs through shunt routes. Therefore, hair follicles are considerable weak spots in our protective sheath against penetration into the body by hydrophilic substances. * We showed that there is a quantitative distinction between follicular penetration and interfollicular diffusion of caffeine in vivo. * These findings are of importance for the development and optimization of topically applied drugs and cosmetics. In addition, such properties must be considered in the development of skin protection measures. Aims: The skin and its appendages are our protective shield against the environment and are necessary for the maintenance of homeostasis. Hypotheses concerning the penetration of substances into the skin have assumed diffusion through the lipid domains of the stratum corneum. It is believed that while hair follicles represent a weakness in the shield, they play a subordinate role in the percutaneous penetration processes. Previous investigation of follicular penetration has mostly addressed methodical and technical problems. Our study utilized a selective closure technique of hair follicle orifices in vivo, for the comparison of interfollicular and follicular absorption rates of caffeine in humans. Methods: Every single hair follicle within a delimited area of skin was blocked with a microdrop of a special varnish-wax-mixture in vivo. Caffeine in solution was topically applied and transcutaneous absorption into the blood was measured by a new surface ionization mass spectrometry (SI/MS) technique, which enabled a clear distinction to be made between interfollicular and follicular penetration of a topically applied substance. Results: Caffeine (3.75 ng ml(-1)) was detected in blood samples, 5 min after topical application, when the follicles remained open. When the follicles were blocked, caffeine was detectable after 20 min (2.45 ng ml(-1)). Highest values (11.75 ng caffeine ml(-1)) were found 1 h after application when the follicles were open. Conclusions: Our findings demonstrate that hair follicles are considerable weak spots in our protective sheath against certain hydrophilic drugs and may allow a fast delivery of topically applied substances.