Targeted Delivery Strategies of Herbal-Based Nanogels: Advancements and Applications.

The objective of this review is to thoroughly investigate herbal nano gels as a promising drug delivery approach for the management of various chronic and acute disorders. Herbal nano gels are a novel and promising drug delivery technique, offering special benefits for better therapeutic efficacy. This review offers a comprehensive analysis of the herbal nano gels with a particular emphasis on their evaluation concerning conventional dosage forms, polymer selection criteria, drug release mechanisms, and applications. The comparison study demonstrates that herbal nano gels have different benefits over conventional dose forms. In the areas of oral administration for improved bioavailability and targeted delivery to the gastrointestinal tract, topical drug delivery for dermatological conditions, and targeted delivery strategies for the site-specific treatment of cancer, inflammatory diseases, and infections, they demonstrate encouraging results in transdermal drug delivery for systemic absorption. A promising platform for improved medication delivery and therapeutic effectiveness is provided by herbal nanogels. Understanding drug release mechanisms further contributes to the controlled and sustained delivery of herbal therapeutics. Some of the patents are discussed and the comparative analysis showcases their superiority over conventional dosage forms, and the polymer selection criteria ensure the design of efficient and optimized formulations. Herbal-based nano gels have become a potential approach for improving drug administration. They provide several advantages such as better stability, targeted delivery, and controlled release of therapeutic components. Herbal nano gels are a promising therapeutic approach with the ability to combat a wide range of conditions like cancer, wound healing and also improve patient compliance.

Development and Evaluation of Nanoformulations Containing Timur Oil and Rosemary Oil for Treatment of Topical Fungal Infections.

The pervasiveness of fungal infections is an issue for skin health globally, and there are a reported 40 million cases in developed and developing countries. Novel drug delivery systems provide better therapeutic efficacy over conventional drug therapy due to their lower side effects and toxicity. Furthermore, combinations of essential oils can represent alternative therapies for fungal infections that are resistant to synthetic drugs. This study is aimed at developing Timur oil into a nanoemulgel and evaluating its antifungal effects. The development of the formulation involved the preparation of a nanoemulsion by the titration method, followed by its evaluation for various physicochemical properties. The antifungal activity of the nanoemulgel against Candida albicans was evaluated. The zone of inhibition was determined using the disk diffusion method. The results show that the developed nanoemulgel has a particle size of 139 ± 6.11 nm, a PDI of 0.309, and a zeta potential of -19.12 ± 2.73 mV. An in vitro drug release study showed a sustained release of 70 ± 0.289% of the drug over a period of 24 h. The % drug permeation across the skin was found to be 79.11 ± 0.319% over 24 h. However, the amount of drug retained in the skin was 56.45 µg/g. The flux for the nanoemulgel was found to be 94.947 µg/cm2/h, indicating a better permeability profile. The nanoemulgel formulation showed a zone of inhibition of 15 ± 2.45 mm, whereas the 1% ketoconazole cream (marketed preparation) exhibited a zone of inhibition of 13 ± 2.13 mm. The results of this study suggest that developed nanoemulgel containing Timur oil and rosemary oil has the potential to be used for treating topical fungal infections caused by Candida albicans.

In-silico, in-vitro and ex-vivo evidence of combining silymarin phytopharmaceutical with piperine, and fulvic acid for enhancing its solubility and permeability.

Non-alcoholic fatty liver disease is one of the leading causes of death worldwide. Even if with such a high mortality there is no definite treatment approved. Thus, there is a need to develop a formulation which can have multiple pharmacological activities. Herbal drugs are among the most promising compounds that act by different pharmacological actions. For increasing the bio-activity of Silymarin we had isolated five active biomarker molecules from silymarin extract (as a Phytopharmaceutical) in our previous work. It possesses lower bioavailability due to poor solubility, lesser permeability and first pass metabolism effect. Therefore, from the literature we had screened two bioavailability enhancers i.e. piperine and fulvic acid for overcoming the drawbacks associated with silymarin. Hence, in this study we had first explored the ADME-T parameters and then evaluated their in-silico activity for different enzymes involved in inflammation and fibrosis. Interestingly, it was found that besides the bioavailability enhancing property, piperine and fulvic acid also shown anti-inflammatory and anti-fibrotic action, particularly more activity was demonstrated by fulvic acid than piperine. Furthermore, the concentration of the bioavailability enhancers i.e. 20% FA and 10% PIP were optimized by QbD assisted solubility studies. Moreover, the percentage release and apparent permeability coefficient of the optimized formulation was found to be 95% and 90%, respectively as compared to 6.54*106 and 1.63*106 respectively by SM suspension alone. Furthermore, it was found that plain rhodamine solution penetrated only up to 10 um whereas, formulation penetrated up to 30 um. Thus, combining these three, can not only increase the bioavailability of silymarin, but might also, increase the physiological action synergistically.

Cannabis Sativa in Phytotherapy: Reappraisal of Therapeutic Potential and Regulatory Aspects.

Cannabis sativa is widely used as a folk medicine in many parts of the globe and has been reported to be a treasure trove of phytoconstituents, including cannabinoids, terpenoids, and flavonoids. Accumulating evidence from various pre-clinical and clinical studies revealed the therapeutic potential of these constituents in various pathological conditions, including chronic pain, inflammation, neurological disorders, and cancer. However, the psychoactive effect and addiction potential associated with cannabis use limited its clinical application. In the past two decades, extensive research on cannabis has led to a resurgence of interest in the clinical application of its constituents, particularly cannabinoids. This review summarizes the therapeutic effect and molecular mechanism of various phytoconstituents of cannabis. Furthermore, recently developed nanoformulations of cannabis constituents have also been reviewed. Since cannabis is often associated with illicit use, regulatory aspects are of vital importance and this review therefore also documented the regulatory aspects of cannabis use along with clinical data and commercial products of cannabis.

Hypothesizing the Green Synthesis of Tamoxifen Loaded Magnetic Nanoparticles for the Treatment of Breast Cancer.

RESEARCH BACKGROUND: Breast cancer is the second leading cause of death all over the world and is not only limited to females but also affects males. For estrogen receptor-positive breast cancer, tamoxifen has been considered the gold-line therapy for many decades. However, due to the side effects associated with the use of tamoxifen, its use is only limited to individuals in high-risk groups and limits its clinical application to moderate and/or lower-risk groups. Thus, there is a necessity to decrease the dose of tamoxifen, which can be achieved by targeting the drug to breast cancer cells and limiting its absorption to other body parts. PROBLEM STATEMENT: Artificial antioxidants used in the formulation preparation are assumed to upsurge the risk of cancer and liver damage in humans. The need of the hour is to explore bio-efficient antioxidants from natural plant sources as they are safer and additionally possess antiviral, anti-inflammatory, and anticancer properties. Objectives of the study and research: The objective of this hypothesis is to prepare tamoxifen-loaded PEGylated NiO nanoparticles using green chemistry, tumbling the toxic effects of the conventional method of synthesis for targeted delivery to breast cancer cells. Significance of the research work: The significance of the work is to hypothesize a green method for the synthesis of NiO nanoparticles that are eco-friendly, cost-effective, decrease multidrug resistance, and can be used for targeted therapy. Garlic extract contains an organosulfur compound (Allicin) which has drug-metabolizing, anti-oxidant, and tumour growth inhibition effects. In breast cancer, allicin sensitizes estrogen receptors, increasing the anticancer efficacy of tamoxifen and reducing offsite toxicity. Thus, this garlic extract would act as a reducing agent and a capping agent. The use of nickel salt can help in targeted delivery to breast cancer cells and, in turn, reduces drug toxicity in different organs. Future directions/recommendations: This novel strategy may aim for cancer management with less toxic agents acting as an apt therapeutic modality.

WITHDRAWN: Cannabis Sativa In Phytotherapy : Reappraisal Of Therapeutic Potential And Regulatory Aspects

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Sulforaphane: A review of its therapeutic potentials, advances in its nanodelivery, recent patents, and clinical trials.

Traditionally, herbal supplements have shown an exceptional potential of desirability for the prevention of diseases and their treatment. Sulforaphane (SFN), an organosulfur compound belongs to the isothiocyanate (ITC) group and is mainly found naturally in cruciferous vegetables. Several studies have now revealed that SFN possesses broad spectrum of activities and has shown extraordinary potential as antioxidant, antitumor, anti-angiogenic, and anti-inflammatory agent. In addition, SFN is proven to be less toxic, non-oxidizable, and its administration to individuals is well tolerated, making it an effective natural dietary supplement for clinical trials. SFN has shown its ability to be a promising future drug molecule for the management of various diseases mainly due to its potent antioxidant properties. In recent times, several newer drug delivery systems were designed and developed for this potential molecule in order to enhance its bioavailability, stability, and to reduce its side effects. This review focuses to cover numerous data supporting the wide range of pharmacological activities of SFN, its drug-related issues, and approaches to improve its physicochemical and biological properties, including solubility, stability, and bioavailability. Recent patents and the ongoing clinical trials on SFN are also summarized.

Menopausal Remediation and Quality of Life (QoL) Improvement: Insights and Perspectives.

Cessation of menstruation, widely known as menopause is a significant transition period in women's life. It leads to the arrest of fertility and creates a depletion of the hormones causing physical, mental, sexual, and social problems which lead to a serious decline in their quality of life. The onset of menopause induces certain sudden changes, while others appear in a phasic manner, henceforth demanding an adequate understanding of its progression, adverse impact on life, and exploration of any remedial measures thereof. Menopause, despite being a natural occurrence, brings in significant changes to women's life, almost sometimes leading to severe debilitation. However, it is still not attended and remains an ignored health issue that warrants the immediate attention of researchers, practitioners, and health policymakers. The present review is an attempt to draw attention towards these women-centric health issues and diligently explores the causes, symptoms and also describes the various procedures for the management of menopausal and postmenopausal syndromes. The review tries to summarise the currently available pharmaceutical interventions and also dwells into herbal and complementary remedies which could ameliorate and provide respite from the etiolating menopausal symptoms.

Cissampelos pareira Linn. ameliorates thyroxin-induced cardiac hypertrophy in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cissampelos pareira extract has been traditionally used in ayruveda as cardiotonic, diuretics and in heart complains but its pharmacological evaluation in thyroxin-induced cardiac hypertrophy has not yet been explored. AIM OF THE STUDY: The aim of this study was to assess the cardioprotective effect of C. pareira root extract in experimentally induced hyperthyroidism in rats. MATERIALS AND METHODS: Male Wistar rats were treated with (i) thyroxin (0.1 mg/kg/day, i.p.) for 30 days, (ii) C. pareira extract (200 mg/kg/day, p.o.) alone for 60 days, (iii) C. pareira extract (100 and 200 mg/kg/day, p.o., respectively) for 30 days then with thyroxin for another 30 days, (iv) thyroxin for 30 days then C. pareira extract (100 and 200 mg/kg/day, p.o., respectively) for another 30 days. At the end of experiment, serum calcineurin, nitric oxide, lactate dehydrogenase, and thiobarbituric acid reactive substance as well as serum and/or myocardial antioxidant enzymes activity were estimated. RESULTS: Hyperthyroid induced cardiotoxicity was characterized by a significant (P<0.001) increase in heart weight/body weight ratio, serum calcineurin, nitric oxide, lactate dehydrogenase and thiobarbituric acid reactive substance levels as well as a significant decrease in serum reduced glutathione, myocardial glutathione peroxidase, glutathione reductase and glutathione-S-transferase levels, which were significantly (P<0.05 and P<0.01) reverted by C. pareira extract treatment. Reversal of histological changes on treatment with C. pareira extract was also supported the biochemical parameters. These results were quite comparable with amlodipine, the standard drug taken in this study. CONCLUSIONS: Treatment with C. pareira extract ameliorates thyroxin-induced oxidative stress and cardiac hypertrophy, probably through amelioration of calcineurin activity and augmentation of antioxidant enzyme activities.

Tulsi oil as a potential penetration enhancer for celecoxib transdermal gel formulations.

The focus of the present study was to develop and evaluate the transdermal system of celecoxib. Transdermal gels composed of carbopol 940 in propylene glycol (PG) containing penetration enhancers. The formulations were characterized by permeation, pharmacokinetics, pharmacodynamics and histopathology. Celecoxib permeation across excised rat skins were statistically (p < 0.05) enhanced by tulsi oil compared to turpentine oil containing formulations. In comparison to orally administered formulations, the pharmacokinetic parameters of gel and control formulations were significantly higher (p < 0.05). The maximum plasma concentration (Cmax) obtained with formulations containing 4% turpentine and 6% tulsi oil was, respectively, 1.52 and 2.41 times higher than the formulations without penetration enhancer. Similarly, area under the curve (AUC) of these formulations was 1.70 and 2.40 times higher than the formulations without penetration enhancers. Anti-inflammatory studies demonstrated a statistically significant (p < 0.05) pharmacodynamics profile for the transdermal gel formulations compared to orally administered and control celecoxib formulations. Histopathological studies revealed some disruption in the epidermis without any toxic effect on the dermis layer of skin by penetration enhancers. In summary, the transdermal gel formulations of celecoxib containing penetration enhancers sustained drug level in the blood and will reduce the dose frequency as required with its conventional oral formulation.

Effect of Cissampelos pareira root extract on isoproterenol-induced cardiac dysfunction.

The aim of this study was to assess the cardioprotective effect of Cissampelos pareira root extract on isoproterenol-induced cardiac dysfunction in rats. Male albino Wistar rats were randomly divided into eight groups and received either normal saline (0.5 ml/kg, intraperitoneally), isoproterenol (5 mg/kg, intraperitoneally), C. pareira (100 and 200 mg/kg, by gavage, respectively) alone, amlodipine (9 mg/kg, by gavage) alone, C. pareira (100 and 200 mg/kg, respectively) + isoproterenol and amlodipine (9 mg/kg) + isoproterenol, once a day for 30 days, respectively. Isoproterenol-induced cardiac dysfunction was characterized by a significant (P < 0.001) increase in the heart weigh/body weight ratio, serum calcineurin, nitric oxide, lactate dehydrogenase, and thiobarbituric acid reactive substance levels, as well as a significant decrease in serum-reduced glutathione, cardiac glutathione peroxidase, glutathione reductase, and glutathione-S-transferase levels, which were significantly (P < 0.05 and P < 0.01) improved by C. pareira treatment. No significant alteration was observed in the group treated with C. pareira alone compared with the control. C. pareira treatment also restored histopathological changes observed in isoproterenol-induced rats. Amlodipine is used as standard drug in this study. Thus, these results suggest that the attenuation of isoproterenol-induced cardiac dysfunction by treatment with ethanolic root extract of C. pareira may be due to amelioration of calcineurin activity and free radical formation, and by augmentation of antioxidant enzymes activities.

Design, development and evaluation of chronomodulated drug delivery systems of amoxicillin trihydrate with enhanced antimicrobial activity.

The present studies entail the formulation development and evaluation of chronomodulated drug delivery system of amoxicillin trihydrate (AMT), which comprises of a bilayer tablet containing a delayed release and a sustained release layer. Direct compression method was employed for the preparation of bilayer matrix tablets containing rational blend of polymers, such as Eudragit-L100 D55 as delayed release polymer and HPMCK4M, HPMCK15 and HPMCK100 are sustained release polymers. In- vitro drug release studies of bilayer tablets observed a good sustained release action with time-dependent burst release after a lag-time of 3 hrs. Evaluation of drug release kinetics from sustained release layer of bilayer tablets followed Higuchi model via quasi-Fickian diffusion mechanism. SEM studies revealed formation of pores on sustained release layer, which confirmed the drug release through diffusion and predominantly by surface erosion mechanism. Evaluation of antimicrobial activity showed a decrease in minimum inhibitory concentration of optimized bilayer tablets vis-à-vis conventional marketed formulation. Accelerated stability studies revealed that the optimized bilayer tablet formulation was found to be stable upto the period of 6 months. Solid state characterization employing FT-IR and DSC studies indicated lack of significant interaction of drug with formulation excipients. Thus, the present studies ratify the suitability of chronomodulated bilayer tablets of AMT for effective management of bacterial infections owing to specific time-dependent drug release, higher gastric protection and enhanced antimicrobial activity.

Reduced bioavailability of tamoxifen and its metabolite 4-hydroxytamoxifen after oral administration with biochanin A (an isoflavone) in rats.

The aim of this study was to investigate the effect of biochanin A (BCA) on the pharmacokinetics of tamoxifen, a substrate of P-glycoprotein (P-gp) and cytochrome 3A (CYP3A), in female rats. The tamoxifen was administered orally (10 mg/kg) without or with oral BCA (100 mg/kg) in female rats. As BCA is an inhibitor of CYP 3A and P-gp it was expected to increase the bioavailability of tamoxifen, a known substrate of CYP3A4/Pgp. Surprisingly, compared with the control group (treated with tamoxifen alone), BCA pretreated animals showed significantly (p < 0.05) decreased area under the plasma concentration-time curve from time zero to time infinity (AUC(0-∞)) and peak tamoxifen concentrations (C(max)). Consequently, the relative bioavailability (RB%) of tamoxifen co-administered with BCA was remarkably decreased compared with the control group. The AUC(0-∞) and C(max) of 4-hydroxytamoxifen in BCA pretreated rats were also significantly (p < 0.05) lower than those from the control group. However, there were no apparent changes in the metabolite ratio (MR; AUC(0-∞) of 4-hydroxytamoxifen to tamoxifen) by co-administration of BCA. If the results of this study are further confirmed by clinical trials, tamoxifen dosages should be adjusted to avoid potential drug interaction when tamoxifen is used clinically in combination with BCA and BCA-containing dietary supplements.

Antimicrobial activity assessment of time-dependent release bilayer tablets of amoxicillin trihydrate

The aim of present study was the assessment of antimicrobial activity of prepared time-dependent release bilayer tablets of amoxicillin trihydrate and in vitro evaluation of drug release by antimicrobial assay using agar plate diffusion method. The bilayer tablets comprised of a delayed and sustained release layer. Direct compression method was used for the preparation of bilayer tablets containing Eudragit-L100 D55 as delayed release polymer, and HPMCK4M and HPMCK15 as sustained release polymers. The prepared bilayer tablets containing amoxicillin trihydrate were evaluated for hardness, thickness, friability, weight variation and drug content. Further, in vitro drug release was assessed by antimicrobial assay using S. aureus and E. coli as test microorganisms. The aliquot samples of in vitro drug release study were found to be effective against both microorganisms for 16 hours due to sustained action. The in vitro drug release study and antimicrobial assay showed that bilayer tablets have sustained release profile of drug delivery with time-dependent burst release after a lag-time of 2 hours. The lower MIC value (2 µg/mL) of prepared bilayer tablets vis-à-vis marketed preparation (5 µg/mL) represented its good antimicrobial activity.

O objetivo do presente estudo foi avaliar a atividade antimicrobiana de formulações de comprimidos de dupla camada contendo amoxicilina triidratada para liberação tempo dependente e avaliação da liberação in vitro do fármaco pelo ensaio de atividade antimicrobiana utilizando o método de difusão em placa de ágar. Os comprimidos de dupla camada consistem em uma camada para liberação retardada e outra sustentada. O método de compressão direta foi usado para a preparação dos comprimidos de dupla camada contendo Eudragit-L 100 D55 como polímero para liberação retardada e HPMCK4M ou HPMCK15 como polímeros para liberação sustentada. As formulações de comprimidos de dupla camada contendo amoxicilina triidratada foram avaliadas quanto a dureza, espessura, friabilidade, variação de peso e conteúdo de fármaco. Além disso, a liberação do fármaco in vitro foi avaliada por ensaio de atividade antimicrobiana usando S. aureus e E. coli como microrganismos teste. A alíquota das amostras do estudo de liberação do fármaco in vitro demonstrou ser efetiva contra ambos os microrganismos por um período de 16 horas devido à ação sustentada. O estudo de liberação do fármaco in vitro e o ensaio de atividade antimicrobiana mostraram que os comprimidos de dupla camada tiveram um perfil de liberação sustentada do fármaco com um pico de liberação após 2 horas de ensaio. O menor valor de MIC (2 ug/mL) dos comprimidos de dupla camada quando comparados à formulação comercial (5 ug/mL) representa uma boa atividade antimicrobiana.

Reassessing bioavailability of silymarin.

Silymarin, a flavonolignan derived from Silybum marianum, possesses diverse pharmacological activities, including hepatoprotective, antioxidant, anti-inflammatory, anticancer, and cardioprotective. Although clinical trials have shown silymarin is safe at high doses (>1500 mg/day) in humans, the pharmacokinetic studies over the past three decades related to absorption, distribution, metabolism, and excretion of silymarin have revealed poor absorption, rapid metabolism, and ultimately poor oral bioavailability. For optimum silymarin bioavailability, issues of solubility, permeability, metabolism, and excretion must be addressed. An array of methods have been described in recent years that can improve its bioavailability, including complexation with ß-cyclodextrins, solid dispersion method, formation of microparticles and nanoparticles, self-microemulsifying drug delivery systems, micelles, liposomes, and phytosomes. This article critically reviews the recent published literature on various techniques for increasing the bioavailability of silymarin.

Isoproterenol-induced cardiomyopathy in rats: influence of Acorus calamus Linn.: A. calamus attenuates cardiomyopathy.

Acorus calamus has been used as a traditional remedy since ancient days but its cardioprotective effect is not yet well characterized. The aim of this study was to assess the effect of A. calamus rhizome extract in isoproterenol-induced cardiomyopathy in rats. Male Wistar rats were treated with normal saline (0.5 ml/kg, i.p.), isoproterenol (5 mg/kg, i.p.), A. calamus (100 and 200 mg/kg, respectively, by gavage) alone, amlodipine (9.0 mg/kg, by gavage) alone, A. calamus (100 and 200 mg/kg, respectively) + isoproterenol and amlodipine (9.0 mg/kg) + isoproterenol, single dose/day for 30 days, respectively. Isoproterenol-induced cardiomyopathy was characterized by a significant (P < 0.001) increase in heart weigh/body weight ratio, calcineurin, nitric oxide, lactate dehydrogenase, and thiobarbituric acid-reactive substance levels as well as a significant (P < 0.001) decrease in reduced glutathione, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase levels. Treatment with A. calamus significantly (P < 0.05 and P < 0.01) attenuated isoproterenol-induced cardiomyopathy. No significant alteration was found in A. calamus-alone groups compared with the vehicle. Amlodipine is used as standard drug in this study. Thus, the result shows that A. calamus attenuates isoproterenol-induced cardiomyopathy. This could be due to attenuating calcineurin activity and oxidative stress.

A study of the chemical composition of black cumin oil and its effect on penetration enhancement from transdermal formulations.

The chemical composition of the solvent extracted fixed oil of black cumin (Nigella sativa L.) seeds was determined by capillary GC and GC/MS. Thirty-two fatty acids (99.9%) have been identified in the fixed oil. The major fatty acids were linoleic acid (50.2%), oleic acid (19.9%), margaric acid (10.3%), cis-11,14-eicosadienoic acid (7.7%) and stearic acid (2.5%). The effect of black cumin oil on in vitro percutaneous absorption of the model lipophilic drug carvedilol was investigated using excised rat abdominal skin. Transdermal flux, permeability coefficient and enhancement factor were calculated for different concentrations of oil in isopropyl alcohol. Black cumin oil (5% v/v) exhibited the highest enhancement in permeation. The increase in the permeability of the drug is due to increased drug diffusivity through the stratum corneum under the influence of black cumin oil. A higher content of linoleic acid (and other unsaturated fatty acids) in the oil has been postulated to be responsible for the enhancement of in vitro percutaneous absorption of the drug.

Patented bioavailability enhancement techniques of silymarin.

The present article dwells in reviewing critically the patents published mainly on the new emerging trends and techniques for increasing the bioavailability of silymarin, the polyphenolic fraction obtained from the seeds of Silybum marianum. The use of this herb for treating various ailments like hepatitis, cirrhosis, jaundice, mushroom and toxin poisoning is well known. But the potential use of this herbal drug is limited due to the poor absorption and poor bioavailability after oral administration The belief that the natural medicines are much safer than synthetic drugs, has gained popularity in recent years and led to tremendous growth of phytopharmaceutical usage and thus the need of improving the bioavailability by various means like complexation, derivatization, solubilization, targeted delivery, controlled delivery and many other miscellaneous techniques.

Mechanism of in vitro percutaneous absorption enhancement of carvedilol by penetration enhancers.

The effect of penetration enhancers like tulsi (basil) oil, eucalyptus oil, clove oil, black cumin oil, oleic acid and Tween 80 on the percutaneous absorption of model lipophilic drug-carvedilol was investigated using excised rat abdominal skin. Transdermal flux, permeability coefficient and enhancement factor were calculated for each penetration enhancer. Black cumin oil (5% v/v) was selected on the basis of its highest enhancement in permeation and was evaluated further for its mode of action using DSC, FTIR and histological studies. The results indicated that the oil shows its action by extraction of lipids from stratum corneum as well as by loosening the hydrogen bonds between ceramides subsequently leading to fluidization of the lipid bilayer.

Improvement in bioavailability of transdermally applied flurbiprofen using tulsi (Ocimum sanctum) and turpentine oil.

Penetration enhancing potential of tulsi and turpentine oil on transdermal delivery of flurbiprofen, a potent non-steroidal anti-inflammatory agent, was investigated. The transdermal permeation rate of flurbiprofen across the rat abdominal skin from binary solvent mixture composition of propylene glycol (PG):isopropyl alcohol (IPA) (30:70%, v/v) was 98.88 microg/cm(2)/h, significantly higher than other binary solvent mixtures. The corresponding steady state plasma concentration, 0.71 microg/ml, was much lower than required steady state plasma concentration of 3-5 microg/ml. Hence influence of tulsi and turpentine oil in the optimized binary solvent mixture along with the increased drug load on the flurbiprofen permeation was evaluated. The magnitude of the flux enhancement factor with turpentine oil and tulsi oil was 2.4 and 2.0 respectively at 5% (v/v) concentration beyond which there was no significant increase in the flux. Addition of 2% (w/v) hydroxypropyl methylcellulose (HPMC), as a thickening agent, resulted in desired consistency for the fabrication of patch with insignificant effect on permeation rate of flurbiprofen. The reservoir type of transdermal patch formulation, fabricated by encapsulating the flurbiprofen reservoir solution within a shallow compartment moulded from polyester backing film and microporous ethyl vinyl acetate membrane, did not modulate the skin permeation of flurbiprofen through rat skin in case of turpentine formulations whereas flux of formulations with tulsi oil was significantly altered. The influence of penetration enhancer and solvents on the anatomical structure of the rat skin was studied. Enhancement properties exhibited by turpentine oil and tulsi oil in optimized binary solvent mixture were superior as compared to solvent treated and normal control groups with negligible skin irritation. The fabricated transdermal patches were found to be stable. The bioavailability of flurbiprofen with reference to orally administered flurbiprofen in albino rats was found to increase by 2.97, 3.80 and 5.56 times with transdermal patch formulation without enhancer, tulsi and turpentine oil formulations, respectively. The results were confirmed by pharmacodynamic studies in rat edema inflammation model.