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Exploring Transdermal Delivery of Traditional Herbal Medicine for Central Nervous System Disorders
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Acne vulgaris is an inflammatory dermatological pathology that affects mostly young people. However, it can also appear in adulthood, mainly in women. It has a high psychosocial impact, not only at the time of active lesions but also due to the consequences of lesions such as scarring and hyperpigmentation. Several factors are involved in the physiopathology of acne and the constant search for active ingredients is a reality, namely phytotherapeutic ingredients. Tea tree oil is an essential oil extracted from Melaleuca alternifolia (Maiden & Betch) Cheel with known antibacterial, anti-inflammatory, and antioxidant properties, making it a candidate for the treatment of acne. This review aims to describe the various properties of tea tree oil that make it a possible ingredient to use in the treatment of acne and to present several human studies that have evaluated the efficacy and safety of using tea tree oil in the treatment of acne. It can be concluded that tea tree oil has good antibacterial, anti-inflammatory, and antioxidant properties that result in a decrease in the number of inflammatory lesions, mainly papules, and pustules. However, given the diversity of study designs, it is not possible to draw concrete conclusions on the efficacy and safety of this oil in the treatment of acne.
Adaptogens are natural (herbs) or synthetic compounds (levamisole) used to maintain stability in human body. The plant based adaptogens were mainly used to enhance the physical endurance and metal health of patients. However, adaptogens are widely studied for their ability to protect and cope up the body against physical, chemical and biological stress and related diseases. Panax ginseng and Withania somnifera are natural adaptogens, used to attenuate stress & related disorders without increasing oxygen consumption. This review deals with a detailed description of adaptogenic potential of Panax ginseng and Withania somnifera in improving human health. It also focuses on the similarity and mechanism of action of Panax ginseng and Withania somnifera as adaptogens on human stress induced disorders.
Various non-invasive administrations have recently emerged as an alternative to conventional needle injections. A transdermal drug delivery system (TDDS) represents the most attractive method among these because of its low rejection rate, excellent ease of administration, and superb convenience and persistence among patients. TDDS could be applicable in not only pharmaceuticals but also in the skin care industry, including cosmetics. Because this method mainly involves local administration, it can prevent local buildup in drug concentration and nonspecific delivery to tissues not targeted by the drug. However, the physicochemical properties of the skin translate to multiple obstacles and restrictions in transdermal delivery, with numerous investigations conducted to overcome these bottlenecks. In this review, we describe the different types of available TDDS methods, along with a critical discussion of the specific advantages and disadvantages, characterization methods, and potential of each method. Progress in research on these alternative methods has established the high efficiency inherent to TDDS, which is expected to find applications in a wide range of fields.
Background
Herbal medicinal material and product need is increasing, and with this increase in the need, it is very much an essential requirement to maintain the quality of them.
Main body
The quality of the herbals is altered by various physical, chemical, and geographical aspects which contribute to the quality of these materials. Apart from that, adulteration is also an increasing concern when it comes to herbal material quality. Various chemical and phytochemical test, analytical techniques, and hyphenated analytical techniques are used for determining the quality aspects of the herbal materials in the herbal pharmaceuticals.
Conclusion
These techniques can be used as quality control tool in assessing the quality of herbal materials and herbal pharmaceuticals.
Background: Acne vulgaris is known as a commonly-seen skin disease with a considerable impact on the quality of life. At present, there have been a growing number of epidemiological, medical, demographic and sociological researches focusing on various influencing factors in the occurrence of acne. Nevertheless, the correlation between environmental factors and acne has yet to be fully investigated.
Objective: To assess the impacts of individual, natural and social environmental factors on acne and to construct a framework for the potential impact of built environment on acne.
Methods: A thorough review was conducted into the published social demographical, epidemiological, and environmental studies on acne through PubMed, Google Scholar and Web of Science, with reference made to the relevant literature.
Results: The influencing factors in acne are classed into four major categories. The first one includes individual socio-economic and biological factors, for example, gender, age, economic level, heredity, obesity, skin type, menstrual cycle (for females), diet, smoking, cosmetics products, electronic products, sleep quality and psychological factors. The second one includes such natural environmental factors as temperature, humidity, sun exposure, air pollution and chloracne. The third one relates to social environment, including social network and social media. The last one includes built environmental factors, for example, population density, food stores, green spaces, as well as other built environment characteristics for transport. Acne can be affected negatively by family history, overweight, obesity, oily or mixed skin, irregular menstrual cycles, sugary food, greasy food, dairy products, smoking, the improper use of cosmetics, the long-term use of electronics, the poor quality of sleep, stress, high temperature, sun exposure, air pollution, mineral oils and halogenated hydrocarbons. Apart from that, there are also potential links between built environment and acne.
Conclusions: It is necessary to determine the correlation between the built environment and acne based on the understanding of the impact of traditional factors (sociology of population and environment) on acne gained by multidisciplinary research teams. Moreover, more empirical studies are required to reveal the specific relationship between built environment and acne.
Multidisciplinary investigations into the pathogenesis of acne have significantly progressed over the past three years. Studies of the etiology of acne from the perspectives, for example, of sebaceous gland biology, sebum, genetics, keratinization, differentiation, hair cycles, immunology, bacteriology, and wound healing have elucidated its pathogenesis. This has led to the development of new therapies and paved the way for advanced studies that will enable the further evolution of acne treatment.
Invasomes are novel vesicular systems that exhibit improved transdermal penetration compared to conventional liposomes. These vesicles contain phospholipids, ethanol, and terpene in their structures; these components confer suitable transdermal penetration properties to the soft vesicles. The main advantages of these nanovesicles lie in their ability to increase the permeability of the drug into the skin and decrease absorption into the systemic circulation, thus, limiting the activity of various drugs within the skin layer. In this paper, several features of invasomes, including their structure, mechanism of penetration, applications, characterization, and potential advantages in dermal drug delivery, are highlighted. Overall, this review suggests that enhanced transdermal penetration of drugs using invasomes provides an appropriate opportunity for the development of lipid vesicular carriers.
Cutibacterium acnes, former Proprionibacterium acnes, is a heterogeneous species including acneic bacteria such as the RT4 strain, and commensal bacteria such as the RT6 strain. These strains have been characterized by metagenomic analysis but their physiology was not investigated until now. Bacteria were grown in different media, brain heart infusion medium (BHI), reinforced clostridial medium (RCM), and in sebum like medium (SLM) specifically designed to reproduce the lipid rich environment of the sebaceous gland. Whereas the RT4 acneic strain showed maximal growth in SLM and lower growth in RCM and BHI, the RT6 non acneic strain was growing preferentially in RCM and marginally in SLM. These differences were correlated with the lipophilic surface of the RT4 strain and to the more polar surface of the RT6 strain. Both strains also showed marked differences in biofilm formation activity which was maximal for the RT4 strain in BHI and for the RT6 strain in SLM. However, cytotoxicity of both strains on HaCaT keratinocytes remained identical and limited. The RT4 acneic strain showed higher inflammatory potential than the RT6 non acneic strain, but the growth medium was without significant influence. Both bacteria were also capable to stimulate β‐defensine 2 secretion by keratinocytes but no influence of the bacterial growth conditions was observed. Comparative proteomics analysis was performed by nano LC‐MS/MS and revealed that whereas the RT4 strain only expressed triacylglycerol lipase, the principal C. acnes virulence factor, when it was grown in SLM, the RT6 strain expressed another virulence factor, the CAMP factor, exclusively when it was grown in BHI and RCM. This study demonstrates the key influence of growth conditions on virulence expression by C. acnesand suggest that acneic and non acneic strains are related to different environmental niches.
What we already know about this topic:
Chronic alcohol use and withdrawal leads to increased pain perception, anxiety, and depression. These aberrant behaviors are accompanied by increased excitatory glutamatergic transmission to, and activity of, the lateral habenula neurons.Vanilloid type 1, or TRPV1, channels are expressed in the habenula and they facilitate glutamatergic transmission. Whether TRPV1 channel plays a role in habenula hyperactivity is not clear.
What this article tells us that is new:
Glutamatergic transmission in the lateral habenula was inhibited by TRPV1 channel antagonists. In vivo, local administration of TRPV1 antagonists into the lateral habenula attenuated hyperalgesia, anxiety, and relapse-like drinking in rats who chronically consumed alcohol.The data suggest that enhanced TRPV1 channel function during withdrawal may contribute to aberrant behavior that promotes relapse alcohol consumption.
Background:
Recent rat studies indicate that alcohol withdrawal can trigger a negative emotional state including anxiety- and depression-like behaviors and hyperalgesia, as well as elevated glutamatergic transmission and activity in lateral habenula neurons. TRPV1, a vanilloid receptor expressed in the habenula, is involved in pain, alcohol dependence, and glutamatergic transmission. The authors therefore hypothesized that TRPV1 contributes to the changes in both the behavioral phenotypes and the habenula activity in alcohol-withdrawn rats.
Methods:
Adult male Long-Evans rats (n = 110 and 280 for electrophysiology and behaviors, respectively), randomly assigned into the alcohol and water (Naïve) groups, were trained to consume either alcohol or water-only using an intermittent-access procedure. Slice electrophysiology was used to measure spontaneous excitatory postsynaptic currents and firing of lateral habenula neurons. The primary outcome was the change in alcohol-related behaviors and lateral habenula activity induced by pharmacologic manipulation of TRPV1 activity.
Results:
The basal frequency of spontaneous excitatory postsynaptic currents and firing of lateral habenula neurons in alcohol-withdrawn rats was significantly increased. The TRPV1 antagonist capsazepine (10 µM) induced a stronger inhibition on spontaneous excitatory postsynaptic currents (mean ± SD; by 26.1 ± 27.9% [n = 11] vs. 6.7 ± 18.6% [n = 17], P = 0.027) and firing (by 23.4 ± 17.6% [n = 9] vs. 11.9 ± 16.3% [n = 12], P = 0.025) in Withdrawn rats than Naive rats. By contrast, the TRPV1 agonist capsaicin (3 μM) produced a weaker potentiation in Withdrawn than Naïve rats (spontaneous excitatory postsynaptic currents: by 203.6 ± 124.7% [n = 20] vs. 415.2 ± 424.3% [n = 15], P < 0.001; firing: 38.1 ± 14.7% [n = 11] vs. 73.9 ± 41.9% [n = 11], P < 0.001). Conversely, capsaicin's actions in Naïve but not in Withdrawn rats were significantly attenuated by the pretreatment of TRPV1 endogenous agonist N-Oleoyldopamine. In Withdrawn rats, intra-habenula infusion of TRPV1 antagonists attenuated hyperalgesia and anxiety-like behaviors, decreased alcohol consumption upon resuming drinking, and elicited a conditioned place preference.
Conclusions:
Enhanced TRPV1 function may contribute to increased glutamatergic transmission and activity of lateral habenula neurons, resulting in the aberrant behaviors during ethanol withdrawal.
Ethno-botanical use and traditional knowledge of plants have been usually recognized all over the world. The outstanding characteristics of extracts obtained from this drug have been technically studied, attributing the main biological activity to its tannin and flavonoid content. Recent study about this drug Adiantum capillus-veneris Linn requires pharmacognostical evidences to develop quality-control methods for raw materials and extracts produced with this plant drug. In this research article macro and micro-scopic studies were proven the authentication of the real drug in which adulteration is allowed in commercial samples of this plant material. The parameters which were mention in this study all are according to WHO guidelines and Indian Pharmacopoeia (IP). The morphological characteristics present in this article can be useful for quick identification of the drug, particularly useful in the case of powdered drug. Physicochemical parameters such as total ash, water soluble ash, acid insoluble ash, loss on drying, percentage of foreign matter and extractive values were determined. Preliminary phytochemical screening in different solvents showed the presence of flavonoids, terpenoids, fats, tannins and phenolic compounds. The various phytochemicals presence in the drug are confirmed by thin layer chromatography (TLC) profile. The study can serve as a valuable source of information and provide suitable standards for the presence of various phytochemicals. The results extracted from this study such as identification, phytochemical investigation etc. could be helpful in future research and uses
Melaleuca alternifolia tea tree oil (TTO) is largely used in cutaneous infections. Clinical observations reported antibacterial, antifungal, and antiviral activities, whereas in vitro experiments ascribed most of biological properties to terpinen-4-ol. Since different plant chemotypes and storage conditions result in variations of chemical composition of commercially available TTO, in this study we investigated the antimicrobial activity and the chemical profile of ten commercially available TTO products. The antimicrobial activity was assessed against Candida glabrata, Herpes simplex virus type 1 (HSV-1), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa grown in planktonic mode or biofilms. Only five out of ten TTO batches reported significant antimicrobial activity. The identified TTO products reduced bacterial survival in biofilms, generated oxidative damage in C. glabrata, and diminished HSV-1 infectivity. GC–MS analysis revealed that all the analyzed TTO batches fitted into the terpinen-4-ol chemotype even if we reported great variability in composition of nine major ISO-specified TTO components. Overall, we were not able to ascribe the antimicrobial activity to the content in terpinen-4-ol. We therefore conclude that the antimicrobial activity of TTO results from complex interaction among different components.
Background:
In recent years, nanoparticles (NPs) including nanostructured lipid carries (NLC) and solid lipid nanoparticles (SLN) captured an increasing amount of attention in the field of transdermal drug delivery system. However, the mechanisms of penetration enhancement and transdermal transport properties of NPs are not fully understood. Therefore, this work applied different platforms to evaluate the interactions between skin and NPs loading triptolide (TPL, TPL-NLC and TPL-SLN). Besides, NPs labeled with fluorescence probe were tracked after administration to investigate the dynamic penetration process in skin and skin cells. In addition, ELISA assay was applied to verify the in vitro anti-inflammatory effect of TPL-NPs.
Results:
Compared with the control group, TPL-NPs could disorder skin structure, increase keratin enthalpy and reduce the SC infrared absorption peak area. Besides, the work found that NPs labeled with fluorescence probe accumulated in hair follicles and distributed throughout the skin after 1 h of administration and were taken into HaCaT cells cytoplasm by transcytosis. Additionally, TPL-NLC could effectively inhibit the expression of IL-4, IL-6, IL-8, IFN-γ, and MCP-1 in HaCaT cells, while TPL-SLN and TPL solution can only inhibit the expression of IL-6.
Conclusions:
TPL-NLC and TPL-SLN could penetrate into skin in a time-dependent manner and the penetration is done by changing the structure, thermodynamic properties and components of the SC. Furthermore, the significant anti-inflammatory effect of TPL-NPs indicated that nanoparticles containing NLC and SLN could serve as safe prospective agents for transdermal drug delivery system.
An ideal drug delivery system fulfills the objective of maximizing therapeutic effect while minimizing toxicity. With the progress in time and advances in science and technology, dosage forms have evolved from simple mixtures and pills, to highly sophisticated systems, which are known as novel drug delivery systems. One of the examples of novel drug delivery system is nanoemulsions [1]. The nanoemulsion are defined as thermodynamically stable, isotropically clear dispersion of two immiscible liquids such as oil and water, stabilized by an interfacial film of surfactant molecule [2]. Nanoemulsion is emulsion with uniform and extremely small droplet size in the range of 20-200 nm [3]. Nanoemulsions do not form spontaneously; to rupture larger droplets into smaller ones, external shear must be applied. As we compared to micro emulsion phases, relatively little is known about creating and controlling nano-emulsions. The first nanoemulsions is prepare in 1940s, it can be of three types i.e., oil-in-water (O/W), water-in-oil (W/O), and bi-continuous [4]. Nanoemulsions are also called as miniemulsions, submicron emulsions and ultrafine emulsions. Research works proves that as compare to the other transdermal drug delivery system nanoemulsion is far more efficient drug delivery system [5]. The major difference between emulsion and nanoemulsion is that the even though emulsion is kinetically stable but thermodynamically unstable, emulsion are cloudy and nanoemulsion is very clear in physical appearance [6].
Low high-density lipoprotein cholesterol (HDL-C) is associated with an increased risk of coronary heart disease (CHD). This study aimed to evaluate the effects of capsaicin intervention on the serum lipid profile in adults with low HDL-C. In a randomized, double-blind, controlled clinical trial, 42 eligible subjects were randomly assigned to the capsaicin (n = 21, 4 mg of capsaicin daily) or to the control group (n = 21, 0.05 mg of capsaicin daily) and consumed two capsaicin or control capsules, which contained the powder of the skin of different peppers, twice daily for three months. Thirty-five subjects completed the trial (18 in the capsaicin group and 17 in the control group). The baseline characteristics were similar between the two groups. Compared with the control group, fasting serum HDL-C levels significantly increased to 1.00 ± 0.13 mmol/L from 0.92 ± 0.13 mmol/L in the capsaicin group (p = 0.030), while levels of triglycerides and C-reactive protein and phospholipid transfer protein activity moderately decreased (all p < 0.05). Other lipids, apolipoproteins, glucose, and other parameters did not significantly change. In conclusion, capsaicin improved risk factors of CHD in individuals with low HDL-C and may contribute to the prevention and treatment of CHD.
Background: The effects of capsaicin on obesity and glucose homeostasis are still controversial and the mechanisms underlying these effects remain largely unknown. This study aimed to investigate the potential relationship between the regulation of obesity and glucose homeostasis by dietary capsaicin and the alterations of gut microbiota in obese diabetic ob/ob mice.
Methods: The ob/ob mice were subjected to a normal, low-capsaicin (0.01%), or high-capsaicin (0.02%) diet for 6 weeks, respectively. Obesity phenotypes, glucose homeostasis, the gut microbiota structure and composition, short-chain fatty acids, gastrointestinal hormones, and pro-inflammatory cytokines were measured.
Results: Both the low- and high-capsaicin diets failed to prevent the increase in body weight, adiposity index, and Lee's obesity index. However, dietary capsaicin at both the low and high doses significantly inhibited the increase of fasting blood glucose and insulin levels. These inhibitory effects were comparable between the two groups. Similarly, dietary capsaicin resulted in remarkable improvement in glucose and insulin tolerance. In addition, neither the low- nor high-capsaicin diet could alter the α-diversity and β-diversity of the gut microbiota. Taxonomy-based analysis showed that both the low- and high-capsaicin diets, acting in similar ways, significantly increased the Firmicutes/Bacteroidetes ratio at the phylum level as well as increased the Roseburia abundance and decreased the Bacteroides and Parabacteroides abundances at the genus level. Spearman's correlation analysis revealed that the Roseburia abundance was negatively while the Bacteroides and Parabacteroides abundances were positively correlated to the fasting blood glucose level and area under the curve by the oral glucose tolerance test. Finally, the low- and high-capsaicin diets significantly increased the fecal butyrate and plasma total GLP-1 levels, but decreased plasma total ghrelin, TNF-α, IL-1β, and IL-6 levels as compared with the normal diet.
Conclusions: The beneficial effects of dietary capsaicin on glucose homeostasis are likely associated with the alterations of specific bacteria at the genus level. These alterations in bacteria induced by dietary capsaicin contribute to improved glucose homeostasis through increasing short-chain fatty acids, regulating gastrointestinal hormones and inhibiting pro-inflammatory cytokines. However, our results should be interpreted cautiously due to the lower caloric intake at the initial stage after capsaicin diet administration.
Eugenol is a hydroxyphenyl propene, naturally occurring in the essential oils of several plants belonging to the Lamiaceae, Lauraceae, Myrtaceae, and Myristicaceae families. It is one of the major constituents of clove (Syzygium aromaticum (L.) Merr. & L.M. Perry, Myrtaceae) oil and is largely used in both foods and cosmetics as a flavoring agent. A large body of recent scientific evidence supports claims from traditional medicine that eugenol exerts beneficial effects on human health. These effects are mainly associated with antioxidant and anti-inflammatory activities. Eugenol has also shown excellent antimicrobial activity in studies, being active against fungi and a wide range of gram-negative and gram-positive bacteria. The aim of this review is to analyze scientific data from the main published studies describing the antibacterial and antifungal activities of eugenol targeting different kind of microorganisms, such as those responsible for human infectious diseases, diseases of the oral cavity, and food-borne pathogens. This article also reports the effects of eugenol on multi-drug resistant microorganisms. On the basis of this collected data, eugenol represents a very interesting bioactive compound with broad spectrum antimicrobial activity against both planktonic and sessile cells belonging to food-decaying microorganisms and human pathogens.
Background
Transdermal drug delivery system (TDDS) was designed to sustain the release and improve the bioavailability of drug and patient compliance. Among the various types of transdermal patches, matrix dispersion type systems disperse the drug in the solvent along with the polymers and solvent is allowed to evaporate forming a homogeneous drug-polymer matrix. The objective of the present study was to design and formulate TDDS of topiramate (TPM) and to evaluate their extended release in vitro and ex vivo.
Materials and Methods
In the present study, an attempt has been made to develop a matrix-type transdermal therapeutic system comprising TPM with different ratios of hydrophilic and hydrophobic polymeric combinations using solvent casting technique.
Results
The physicochemical compatibility of the drug and the polymers was studied by Fourier transform infrared spectroscopy. The results obtained showed no physical-chemical incompatibility between the drug and the polymers. The patches were further subjected to various physical evaluations along with the ex vivo permeation studies using pig ear skin.
Conclusions
On the basis of results obtained from the physical evaluation and ex vivo studies the patches containing the polymers, that is, Eudragit L 100 and polyvinylpyrrolidone, with oleic acid as the penetration enhancer were considered as the best formulations for the transdermal delivery of TPM.
The sebaceous gland is most commonly found in association with a hair follicle. Its traditional function is the holocrine production of sebum, a complex mixture of lipids, cell debris, and other rather poorly characterized substances. Due to the gland’s central role in acne pathogenesis, early research had focused on its lipogenic activity. Less studied aspects of the sebaceous gland, such as stem cell biology, the regulation of cellular differentiation by transcription factors, the significance of specific lipid fractions, the endocrine and specially the neuroendocrine role of the sebaceous gland, and its contribution to the innate immunity, the detoxification of the skin, and skin aging have only recently attracted the attention of researchers from different disciplines. Here, we summarize recent multidisciplinary progress in sebaceous gland research and discuss how sebaceous gland research may stimulate the development of novel therapeutic strategies targeting specific molecular pathways of the pathogenesis of skin diseases.
Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use.
In spite of incredible advances in modern science, technology and allopathic medicine a large we are unable to provide quality healthcare to all. Traditional medicine particularly herbal medicine considered as a major healthcare provider around the globe particularly in rural and remote areas. A large section of people depends on such medicine for their primary healthcare mainly in underdeveloped or developing countries. Indian traditional medicinal system like Ayurveda, Siddha and Unani has a very rich history of their effectiveness; modern research also acknowledged the importance of such medicine. Indian traditional medicine or medicinal plants are also considered as a vital source of new drug. Mainstreaming of such medicine is important for the people. Several steps have been taken in India to promote such medicine and to integrate them into clinical practice. Evidence based incorporation of Indian traditional medicine in clinical practice will help to provide quality healthcare to all.
Transdermal drug delivery system (TDDS) provides a means to sustain drug release as well as reduce the intensity of action and thus reduce the side effects associated with its oral therapy. Transdermal drugs are self-contained, discrete dosage form . It delivers a drug through intact skin at a controlled rate into the systemic circulation. Delivery rate is controlled by the skin or membrane in the delivery system .A sophisticated complex drug delivery system difficult to formulate. It requires specialized manufacturing process/equipment. Formulated to meet specific biopharmaceutical and functional characteristics. The materials of construction, configuration and combination of the drug with the proper cosolvent, excipient, penetration enhancer, and membrane are carefully selected and matched to optimize adhesive properties and drug delivery requirements. Transdermal drug delivery - an approach used to deliver drugs through the skin for therapeutic use as an alternative to oral, intravascular, subcutaneous and transmucosal routes. Various transdermal drug delivery technologies are described including the use of suitable formulations, carriers and penetration enhancers. The most commonly used transdermal system is the skin patch using various types of technologies. Transdermal technologies may be applied for several categories of pharmaceuticals used for the treatment of disorders of the skin or for systemic effect to treat diseases of other organs. Several transdermal products and applications include hormone replacement therapy, management of pain, angina pectoris, smoking cessation and neurological disorders such as Parkinson's disease. Formulated to deliver the drug at optimized rate into the systemic circulation should adhere to the skin for the expected duration should not cause any skin irritation and/or sensitization ,Enhancing bioavailability via bypassing first pass metabolism ,Minimizing pharmaco-kinetic peaks and troughs , Improving tolerability and dosing Increasing patient compliance in Continuous delivery.
In this work, two procedures for fabrication of polymeric microneedles based on direct photolithography, without any etching or molding process, are reported. Polyethylene glycol
(average molecular weight 250 Da), casted into a silicone vessel and exposed to ultraviolet light
(365 nm) through a mask, cross-links when added by a commercial photocatalyzer. By changing
the position of the microneedles support with respect to the vessel, different shapes and lengths
can be achieved. Microneedles from a hundred microns up to two millimeters have been obtained
just tuning the radiation dose, by changing the exposure time (5–15 s) and/or the power density
(9–18 mW/cm2) during photolithography. Different microneedle shapes, such as cylindrical, conic
or lancet-like, for specific applications such as micro-indentation or drug delivery, are demonstrated
The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies.
The sequence of events and mechanisms leading to the development of the primary acne lesion, the comedone, is revisited. Recent knowledge obtained both from lineage tracing experiments in the mouse and the pilosebaceous response to xenobiotics in humans provides robust models for further understanding key biological events at the cellular roots of comedogenesis. The focus is set on the LRIG1+ sebaceous stem cells in the isthmus of the pilosebaceous duct. The master switch that transforms a normally functioning sebaceous gland into a microcomedone and the hierarchy of factors involved in this process are reviewed. The key strategic target in acne care appears to be the naïve pilosebaceous follicle that is not involved yet in the acne cycle. The prevention of the comedone switch implies that the key switching factors are adequately controlled in the long term. © 2015 S. Karger AG, Basel.
Chronic unexplained cough triggered by environmental irritants is characterized by increased cough reflex sensitivity, which can be demonstrated by means of inhaled capsaicin. Topical capsaicin can be used to improve non-allergic rhinitis and intestinal hypersensitivity and to reduce neuropathic pain.
We established whether an oral intake of natural capsaicin (chilli) could desensitize the cough reflex and improve unexplained coughing.
Twenty-four patients with irritant-induced, unexplained chronic cough and 15 controls were included in the study. For 4 weeks, the participants took capsules with pure capsaicin, and for 4 weeks, they took placebo capsules. The protocol was crossover, randomized, and double blind. Cough sensitivity during the study was evaluated by a standardized capsaicin inhalation cough test that assessed the capsaicin concentration required to reach two coughs (C2) and five coughs (C5). Participants were also administered questionnaires on cough and cough-related symptoms.
Three patients withdrew before the study end, one during the active treatment period and two during the placebo period. After treatment with capsaicin, the thresholds for C2 were higher (improved) both in patients (p < 0.020) and in controls (p < 0.0061) compared to after the placebo period. Among patients, the concentration needed to reach C2 (p < 0.0004) and C5 (p < 0.0009) increased after the period with the active substance compared to cough thresholds at baseline. The cough symptom scores improved after 4 weeks of active treatment (p < 0.0030) compared to the baseline scores.
Capsaicin powder taken orally decreased capsaicin cough sensitivity and cough symptoms. The findings suggest a desensitization of the cough-sensitive transient receptor potential vanilloid-1 (TRPV1).
Copyright © 2014. Published by Elsevier Ltd.
Essential oil distilled from Melaleuca alternifolia leaves, commonly known as tea tree oil, is well known for its biological activity, principally its antimicrobial properties. However, many samples are adulterated with other, cheaper essential oils such as eucalyptus oil. Current methods of detecting such adulteration are costly and time-consuming, making them unsuitable for rapid authentication screening. This study investigated the use of mid-infrared (MIR) spectroscopy for detecting and quantifying the level of eucalyptus oil adulteration in spiked samples of pure Australian tea tree oil. To confirm the authenticity of the tea tree oil samples, GC-MS analysis was used to profile 37 of the main volatile constituents present, demonstrating that the samples conformed to ISO specifications. Three chemometric regression techniques (PLSR, PCR and SVR) were trialled on the MIR spectra, along with a variety of pre-processing techniques. The best-performing full-wavelength PLSR model showed excellent prediction of eucalyptus oil content, with an R²CV of 0.999 and RMSECV of 1.08% v/v. The RMSECV could be further improved to 0.82% v/v through a moving window wavenumber optimisation process. The results suggest that MIR spectroscopy combined with PLSR can be used to predict eucalyptus oil adulteration in Australian tea tree oil samples with a high level of accuracy.
Despite the rising global incidence of central nervous system (CNS) disorders, CNS drug development remains challenging, with high costs, long pathways to clinical use and high failure rates. The CNS is highly protected by physiological barriers, in particular, the blood–brain barrier and the blood–cerebrospinal fluid barrier, which limit access of most drugs. Biomaterials can be designed to bypass or traverse these barriers, enabling the controlled delivery of drugs into the CNS. In this Review, we first examine the effects of normal and diseased CNS physiology on drug delivery to the brain and spinal cord. We then discuss CNS drug delivery designs and materials that are administered systemically, directly to the CNS, intranasally or peripherally through intramuscular injections. Finally, we highlight important challenges and opportunities for materials design for drug delivery to the CNS and the anticipated clinical impact of CNS drug delivery. The central nervous system is protected by tightly regulated physiological barriers, which make drug delivery into the brain and spinal cord very challenging. This Review discusses the pathophysiological changes that complicate drug delivery into the central nervous system and examines materials-based strategies to bypass or overcome these barriers for drug delivery.
Background:
Trastuzumab has had a major impact on the treatment of human epidermal growth factor receptor 2 (HER2) positive breast cancer patients. However, it is associated with cardiotoxicity, expressed as an asymptomatic decrease in left ventricular ejection fraction (LVEF) and less often as clinical HF. The aim of this meta-analysis is to identify the association of conventional cardiovascular risk factors with the development of trastuzumab-induced cardiotoxicity (TIC).
Methods:
A literature search of PubMed was conducted to identify studies examining the association between cardiovascular risk factors and TIC. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated examining the odds of developing TIC for each of the risk factors.
Results:
A total of 35 studies were included in the analysis. Age (OR:0.7; 95%CI 0.318-1.09; P= 0.0004), hypertension (OR:0.69; 95%CI 0.26-1.12; P = 0.001), smoking(OR:0.35; 95%CI 0.01- 0.69; P = 0.038), diabetes mellitus (OR:0.44; 95%CI 0.24- 0.68; P = 0.0001) and family history of CAD (OR:5.51, 95%CI 1.76-17.25; P< 0.00001)were significantly associated with the development of cardiotoxicity. Known history of CAD (OR: 3.72; 95%CI 2.11-6.57; P = 0.0005) was also associated with the development of TIC.
Conclusion(s):
Identifying women at risk for TIC have several important potential applications. Clinicians may decide to assess LVEF more frequently in patients at highest risk for TIC in order to detect LV systolic dysfunction earlier. Additionally, this could help identify patients who would benefit most from prophylactic therapy for preventing TIC.
This paper reports for the first time the possible formation of a novel room temperature therapeutic deep eutectic solvent (THEDES) of risperidone (RIS) with some fatty acids, namely capric acid (C10; CA), lauric acid (C12; LA), and myristic acid (C14; MA). All mixtures of RIS and MA yielded a solid or pasty-like solid and were readily discarded. Some of the prepared THEDESs from RIS and CA or LA have spontaneously transformed into a transparent liquid, without any precipitate at room temperature by simple physical mixing of the components. From the DSC thermograms, phase diagrams of the eutectic systems were constructed and the lowest obtained melting point for a RIS:CA mixture was 17°C at 40:60% w/w ratio. While 22°C was recorded as the lowest melting point for RIS:LA at a ratio of 30:70% w/w, solubility improvement of RIS was up to 70,000-fold compared with water. Freeze-drying microscopy provided valuable information regarding the phase change and transitions the drug undergoes as a function of temperature and it clarifies the interpretation of the DSC results and provides valuable evidence of drug crystals co-melting within the fatty acid base. The presence of natural fatty acid as one component of THEDES and the depression in the melting point significantly (P < 0.05) enhanced RIS skin permeation. Rheological studies showed a viscosity temperature dependency of the DES and well fitted to the Arrhenius equation. Application of the obtained THEDES on the shaved skin of rats revealed the absence of any irritation or edema effects.
Clinical trials involving brain disorders are notoriously difficult to set up and run. Innovative ways to develop effective prevention and treatment strategies for central nervous system (CNS) diseases are urgently needed. New approaches that are likely to renew or at least modify the paradigms used so far have been recently proposed. Quantitative systems pharmacology (QSP) uses mathematical computerized models to characterize biological systems, disease processes and CNS drug pharmacology. Integrated experimental medicine should increase the probability and predictability of success while controlling clinical trials costs. Finally, the societal perspective and patient empowerment also offer additional approaches to demonstrate the benefit of a new drug in the CNS field.
Background:
The role of skin microbiota in acne remains to be fully elucidated. Initial culture-based investigations were hampered by growth rate and selective media bias. Even with less biased genomic methods, sampling, lysis and methodology, the task of describing acne pathophysiology remains challenging. Acne occurs in sites dominated by Cutibacterium acnes (formerly Propionibacterium acnes) and Malassezia species, both of which can function either as commensal or pathogen.
Objectives:
This article aims to review the current state of the art of the microbiome and acne.
Methods:
The literature regarding the microbiome and acne was reviewed.
Results:
It remains unclear whether there is a quantitative difference in microbial community distribution, making it challenging to understand any community shift from commensal to pathogenic nature. It is plausible that acne involves (i) change in the distribution of species/strains, (ii) stable distribution with pathogenic alteration in response to internal (intermicrobe) or external stimuli (host physiology or environmental) or (iii) a combination of these factors.
Conclusions:
Understanding physiological changes in bacterial species and strains will be required to define their specific roles, and identify any potential intervention points, in acne pathogenesis and treatment. It will also be necessary to determine whether any fungal species are involved, and establish whether they play a significant role. Further investigation using robust, modern analytic tools in longitudinal studies with a large number of participants, may make it possible to determine whether the microbiota plays a causal role, is primarily involved in exacerbation, or is merely a bystander. It is likely that the final outcome will show that acne is the result of complex microbe-microbe and community-host interplay.
Background:
The European Pharmacopoeia as well as further legal provisions contain rules for the assessment of potential residues and contaminants in herbal substances and preparations used for the production of herbal medicinal products, e.g. for the assessment of pesticide residues, heavy metals and other elemental impurities, mycotoxins and microorganisms. As a potential contamination caused by weeds, the occurrence of pyrrolizidine alkaloids is being discussed for several years which lead to measures of health authorities limiting the PA content in herbal medicinal products and to measures of industry consisting of reducing the probability of PA occurrence in medicinal plants and the respective products.
Conclusion:
In this context and with regard to all kinds of potential residues or contaminants, collection and evaluation of data from daily analytical practice of manufacturers and suppliers is useful for the assessment of the situation and the definition of testing strategies.
Drug encapsulated biodegradable polymeric nanoparticles are suitable for lung delivery of therapeutic molecules. The objective of the current study was to co-encapsulate a hydrophilic drug (theophylline) and a lipophilic drug (budesonide) in poly(lactic acid) (PLA) nanoparticles for pulmonary drug delivery. PLA nanoparticles were produced using a double emulsification solvent diffusion method and characterized for their particle size, zeta potential, drug loading, in vitro drug release, interactions with airway epithelial cell line (16HBE14o-) and in vitro deposition properties upon nebulization. The spherically-shaped mono- and co-encapsulated PLA nanoparticles were observed to have a particle size of 190–400 nm and a zeta potential of −10 to −16mV. Sustained drug release over 24 h was observed from the nanoparticles into a mixture of simulated lung fluid and methanol (1:1), measured using Franz diffusion cells and when assessed for permeability using 16HBE14o-cells. There was no significant reduction in cell viability after 24 h exposure to drug-encapsulated nanoparticles at nebulized concentrations (p > 0.05). Nebulization of co-encapsulated nanoparticles resulted in a fine particle fraction of 75% and 48% for theophylline and budesonide, respectively. From these observations it can be concluded that budesonide and theophylline drug-loaded PLA nanoparticles are suitable drug delivery systems for combination therapy of asthma and COPD.
Background
Due to a variety of factors to affect the herb quality, the exsiting quality management model is unable to evaluate the process control. The development of the concept of "quality marker" (Q-marker) lays basis for establishing an independent process quality control system for herbal products.
Hypothesis/Purpose
To ensure the highest degree of safety, effectiveness and quality process control of herbal products, it is aimed to establish a quality transitivity and traceability system of quality and process control from raw materials to finished herbal products.
Study Design
Based on the key issues and challenges of quality assessment, the current status of quality and process controls from raw materials to herbal medicinal products listed in Pharmacopoeia were analyzed and the research models including discovery and identification of Q-markers, analysis and quality management of risk evaluation were designed.
Methods
Authors introduced a few new technologies and methodologies, such as DNA barcoding, chromatographic technologies, fingerprint analysis, chemical markers, bio-responses, risk management and solution for quality process control.
Results
The quality and process control models for herbal medicinal products were proposed and the transitivity and traceability system from raw materials to the finished products was constructed to improve the herbal quality from the entire supply and production chain.
Conclusion
The transitivity and traceability system has been established based on quality markers, especially on how to control the production process under Good Engineering Practices, as well as to implement the risk management for quality and process control in herbal medicine production.
A wide range of biomedical materials have been proposed to meet the different needs for controlled oral or intravenous drug delivery. The advantages of oral delivery such as self-administration of...
Obesity-induced inflammation contributes to the development of metabolic disorders such as insulin resistance, type 2 diabetes, fatty liver disease, and cardiovascular disease. In this study, we investigated whether the combination of eicosapentaenoic acid (EPA) and capsaicin could protect against high-fat diet (HFD)-induced obesity and related metabolic disorders. The experiments were performed using male C57BL/6J mice that were fed one of the following diets for 10 weeks: standard chow (5.3% fat content) (normal group), a HFD (32.0% fat content) (HFD group), or a HFD supplemented with either 4% (w/w) EPA (EPA group) or a combination of 4% (w/w) EPA and 0.01% (w/w) capsaicin (EPA+Cap group). Our results indicated that the body, fat and liver tissue weights and levels of serum glucose, insulin, total cholesterol, triglyceride, high-density lipoprotein-cholesterol, aspartate aminotransferase, and alanine aminotransferase were significantly higher in HFD group mice than in normal group mice (p<0.05 in all cases). However, the body and fat tissue weights and serum glucose levels and homeostasis model assessment of insulin resistance were significantly lower in EPA+Cap group mice group than in HFD and EPA group mice (p<0.05 in all cases). Thus, our study suggests that the combination of EPA and capsaicin might be beneficial for delaying the progression of obesity-related metabolic dysregulation and subsequent complications.
Graphical Abstract Fullsize Image
Chronic pruritus remains a central societal issue because of its high occurrence and the substantial decrease in quality of life it may cause to affected individuals. Not only dermatological conditions, but also systemic, neurological, or psychiatric diseases may lead to chronic pruritus. Additionally, various underlying conditions may coexist or the cause may be unknown. Due to its heterogeneity, the therapeutic approach is complex and remains a challenge for the clinician. Basic measures such as emollients to avoid xerosis and treatment of the underlying disease should be initiated regardless of the duration of the symptom. Depending on the indication, other topical (e.g., calcineurin inhibitors, topical corticosteroids, capsaicin) and systemic agents (immunosuppressive drugs, gabapentinoids, antidepressants, mu-opioid receptor antagonists) may provide further relief. Additionally, accompanying disorders such as sleep impairment, depression, or anxiety should also be treated. New insights into pathways involved in the development and maintenance of chronic pruritus have led in the past years to the development of a considerable number of novel antipruritic drugs. Several randomized controlled trials have been recently completed or are currently underway testing biological compounds with promising approaches. These include antagonists for nerve growth factor, neuropeptides, histamine 4 receptors, certain interleukin receptors, and opioid receptors.
Poincianella pyramidalis (Tul.) L.P. Queiroz, known as “catingueira,” is a typical species of Caatinga and used in Brazilian folk medicine as anti-inflammatory, antipyretic, diuretic and expectorant. Pharmacological analyses confirmed his activity as anti-inflammatory, antimicrobial and in gastrointestinal disorders. This paper aimed to perform a thermoanalytical characterization of the herbal drugs obtained from P. pyramidalis leaves in different particle sizes. The leaves were dried, pulverized and separated into different granulometric ranges: 50–100, 100–200, 200–400 and <400 mesh. The samples were characterized by thermogravimetry (TG) at different atmospheres and heating rates, determination of the kinetic degradation parameters by Ozawa model, differential thermal analysis (DTA), pyrolysis coupled to gas chromatography interfaced with mass spectrometry (Pyr-GC/MS) and multivariate analysis. TG curves of the samples showed the presence of six thermal decomposition events, with greater mass loss (25.91–35.66%) in the range of 247–398 °C. The thermal degradation proved to be a reaction of zero order, with a decrease in enthalpy and frequency factor with decreasing the granulometric range. DTA curves showed three exothermic events, with peaks around 350, 460 and 490 °C, with variation in enthalpy values. With the Pyr-GC/MS were evidenced different profiles according to the temperature. Principal component analysis of pyrolysis data from samples at different temperatures was able to represent the total variability within the first two principal components, revealing differences between the granulometric ranges. The analytical and statistical techniques used were able to trace characteristic profiles of the herbal drugs, elucidating the differences in each granulometric range.
Objectives
To investigate the long-term safety and tolerability of capsaicin 8% patch repeat treatment in nondiabetic patients with peripheral neuropathic pain.
Methods
A prospective, open-label, observational study in patients with postherpetic neuralgia, posttraumatic or postsurgical nerve injury, HIV-associated distal sensory polyneuropathy, or other peripheral neuropathic pain, and average daily pain score ≥4, who received ≤6 capsaicin 8% patch treatments over 52 weeks according to clinical need (retreatment at 9 to 12 wk intervals). Sensory testing and analgesic effectiveness were assessed using “bedside tests” and Brief Pain Inventory (question 5).
Results
Overall, 306 patients received treatment. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were reported by 252 (82.4%) and 207 (67.6%) patients. Application site pain was the most common drug-related TEAE (n=112, 36.6%); no drug-related serious TEAEs were reported. Sensory category shift analyses from baseline to end of study (EoS) in patients attending at least 2 sensory visits (n=278 for all tests except warm, n=277) found sensory deterioration/loss in at least 1 modality in 50.4% (n=140); deterioration/loss in 1, 2, 3, 4, or 5 modalities occurred in 26.6% (n=74), 14.0% (n=39), 5.8% (n=16), 2.5% (n=7), and 1.4% (n=4) cases. Newly emergent hyperesthesia or allodynia was apparent in 1.1% to 3.6% of the cases (depending on modality) by EoS. Between 25.2% and 32.0% of patients reported improvement in a sensory modality by EoS. Average daily pain was 6.6 and 4.7 at baseline and month 12.
Conclusions
Generally, capsaicin 8% patch repeat treatment over 52 weeks was well tolerated, with variable alteration in sensory function and minimal chance of complete sensory loss.
Ginseng, an herbaceous plant, belonging to the family Araliaceae is a traditional medicinal herb. Also, it is emerging as a functional food and potent adjunct medicine. Saponin ginsenosides (protopanaxadiol and protopanaxatriol) are the signature phytochemicals of this plant. With the surfacing of scientific validations, ginseng is gaining unprecedented attention from consumers as well as researchers. As a number of drug-herb interaction-caused health issues have emerged, the medicinal relevance of this plant has been critically assessed here. In this regard, the recent publications on health benefits of ginseng have been extracted from NCBI and ScienceDirect database. The claimed antioxidant, anti-inflammation, anti-fatigue, antidiabetic, antitumor, immunomodulation, anti-obesity, cardioprotective, antimicrobial, neuroprotective and aphrodisiac properties have been analyzed. This review presents a fair assessment and insights on complementary and alternative medicine (CAM) potential of this herb.
Temporomandibular joint disorder (TMD) is a complex musculoskeletal disorder that presents with pain, limited jaw opening, and abnormal noises in the temporomandibular joint. Despite the significant impact that TMD has in terms of suffering and financial burden, relatively few new treatments have emerged; therefore, development of novel treatments to treat TMD pain remains a high priority. The rationale of this study was to use a double-blind, vehicle-controlled clinical trial to evaluate the effects of a high-concentration (8%) capsaicin cream on TMD. This is based on the hypothesis that targeting TRP vanilloid subfamily member 1 (TRPV1) for pain control may provide a novel method for pain relief in TMD patients. TRPV1 is primarily expressed on a population of nociceptive-specific neurons and provides a candidate target for the development of pain treatments. Capsaicin is the primary agonist for TRPV1 and has been used previously in relatively low doses (0.025% to 0.075%) as a therapeutic for a variety of pain disorders, including postherpetic neuralgia and osteoarthritis; however, analgesic efficacy remains equivocal. TMD and healthy control subjects were assigned to either an active capsaicin or vehicle control group. The treatments were applied for 2 h and then removed. Quantitative sensory testing (QST) was completed prior to drug application (baseline), 2 h after drug application, and 1 wk later. Perceived pain intensity was measured using a visual analog scale (VAS) following capsaicin or vehicle cream application. Significantly lower pain was reported in the week after application in the capsaicin-treated TMD subjects. For QST measures, there was a decreased thermal pain threshold 2 h after capsaicin application for both the control and TMD groups, but this resolved within a week. Capsaicin had no effect on pressure pain threshold or mechanical sensitivity in both TMD and healthy individuals. This study demonstrates that 8% topical capsaicin therapy is a relatively safe, simple, and effective treatment for patients with TMD.
Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involves drug transport to viable epidermal and or dermal tissues of the skin for local therapeutic effect while a very major fraction of drug is transported into the systemic blood circulation. The adhesive of the transdermal drug delivery system is critical to the safety, efficacy and quality of the product. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive methods of drug delivery. Several important advantages of transdermal drug delivery are limitation of hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. This article provides an overview of types of Transdermal patches, methods of preparation and its physicochemical methods of evaluation.
Introduction:
Transdermal drug delivery is the movement of drugs across the skin for absorption into the systemic circulation. Transfer of the drug can occur via passive or active means; passive transdermal products do not disrupt the stratum corneum to facilitate delivery whereas active technologies do. Due to the very specific physicochemical properties necessary for successful passive transdermal drug delivery, this sector of the pharmaceutical industry is relatively small. There are many well-documented benefits of this delivery route however, and as a result there is great interest in increasing the number of therapeutic substances that can be delivered transdermally. Areas Covered: This review discusses the various transdermal products that are currently/have been marketed, and the paths that led to their success, or lack of. Both passive and active transdermal technologies are considered with the advantages and limitations of each highlighted. In addition to marketed products, technologies that are in the investigative stages by various pharmaceutical companies are reviewed. Expert Opinion: Passive transdermal drug delivery has made limited progress in recent years, however with the ongoing intense research into active technologies, there is great potential for growth within the transdermal delivery market. A number of active technologies have already been translated into marketed products, with other platforms including microneedles, rapidly progressing towards commercialisation.
With the advent of new era of pharmaceutical dosage forms, transdermal drug delivery system (TDDS) established itself as an integral part of novel drug delivery systems. Transdermal patches are polymeric formulations which when applied to skin deliver the drug at a predetermined rate across dermis to achieve systemic effects. Transdermal dosage forms, though a costly alternative to conventional formulations, are becoming popular because of their unique advantages. Controlled absorption, more uniform plasma levels, improved bioavailability, reduced side effects, painless and simple application and flexibility of terminating drug administration by simply removing the patch from the skin are some of the potential advantages of transdermal drug delivery. Development of controlled release transdermal dosage form is a complex process involving extensive efforts. This review article describes the methods of preparation of different types of transdermal patches viz., matrix patches, reservoir type, membrane matrix hybrid patches, drug-in-adhesive patches and micro reservoir patches. In addition, the various methods of evaluation of transdermal dosage form have also been reviewed.