Co-Processed Crystalline Solids of Ivermectin with Span® 60 as Solubility Enhancers of Ivermectin in Natural Oils.

Despite being discovered over five decades ago, little is still known about ivermectin. Ivermectin has several physico-chemical properties that can result in it having poor bioavailability. In this study, polymorphic and co-crystal screening was used to see if such solid-state modifications can improve the oil solubility of ivermectin. Span® 60, a lipophilic non-ionic surfactant, was chosen as co-former. The rationale behind attempting to improve oil solubility was to use ivermectin in future topical and transdermal preparations to treat a range of skin conditions like scabies and head lice. Physical mixtures were also prepared in the same molar ratios as the co-crystal candidates, to serve as controls. Solid-state characterization was performed using X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The FTIR spectra of the co-crystal candidates showed the presence of Span® 60's alkyl chain peaks, which were absent in the spectra of the physical mixtures. Due to the absence of single-crystal X-ray data, co-crystal formation could not be confirmed, and therefore these co-crystal candidates were referred to as co-processed crystalline solids. Following characterization, the solid-state forms, physical mixtures and ivermectin raw material were dissolved in natural penetration enhancers, i.e., avocado oil (AVO) and evening primrose oil (EPO). The co-processed solids showed increased oil solubility by up to 169% compared to ivermectin raw material. The results suggest that co-processing of ivermectin with Span® 60 can be used to increase its oil solubility and can be useful in the development of oil-based drug formulations.

Investigation and Evaluation of the Transdermal Delivery of Ibuprofen in Various Characterized Nano-Drug Delivery Systems.

The aim was to assess the suitability of three nano-based transdermal drug delivery systems containing ibuprofen: a nano-emulsion, a nano-emulgel, and a colloidal suspension with ibuprofen-loaded nanoparticles. Understanding the transdermal delivery of ibuprofen using nano-based drug delivery systems can lead to more effective pain relief and improved patient compliance. Characterization tests assessed the suitability of the developed drug delivery systems. Membrane release and skin diffusion studies, along with tape stripping, were performed to determine drug release and skin permeation of ibuprofen. In vitro cytotoxicity studies on HaCaT cells were conducted using MTT and neutral red assays to evaluate the safety of the developed drug delivery systems. Characterization studies confirmed stable drug delivery systems with ideal properties for transdermal delivery. Membrane release studies demonstrated the successful release of ibuprofen. In vitro skin diffusion experiments and tape stripping, detecting ibuprofen in the receptor phase, stratum corneum-epidermis, and epidermis-dermis, indicating successful transdermal and topical delivery. The in vitro cytotoxicity studies observed only minor cytotoxic effects on HaCaT cells, indicating the safety of the developed drug delivery systems. The investigation demonstrated promising results for the transdermal delivery of ibuprofen using the developed drug delivery systems, which contributes to valuable insights that may lead to improved pain management strategies.

Comparative study on the topical and transdermal delivery of diclofenac incorporated in nano-emulsions, nano-emulgels, and a colloidal suspension.

Transdermal delivery of active pharmaceutical ingredients (APIs) can be challenging, since the skin possesses a rate-limiting barrier, which may be overcome when APIs possess certain ideal physicochemical properties. The lack thereof would require that APIs be included in drug delivery vehicles to enhance skin permeation. Hence, diclofenac was incorporated into various drug delivery vehicles (i.e., nano-emulsions, nano-emulgels, and a colloidal suspension containing drug-loaded nanoparticles) to investigate the transdermal delivery thereof, while nano-emulsions and nano-emulgels had varying concentrations of evening primrose oil (EPO). The aim of the study was to compare the topical and transdermal diclofenac delivery from the different types of vehicles and to investigate the influence the different EPO concentrations had on diclofenac delivery. After characterization, membrane release studies were performed (to determine whether the API was successfully released from the vehicle) followed by in vitro skin diffusion studies and tape stripping (to establish whether the vehicles assisted the API in reaching the target site (transdermal delivery)). Lastly, cytotoxicity studies were conducted via methyl thiazolyl tetrazolium (MTT) and neutral red (NR) assays on human keratinocyte (HaCaT) cells. Results showed minimal cytotoxic effects at concentrations equivalent to that which had permeated through the skin, while the membrane release and in vitro skin diffusion studies indicated that the nano-emulsions and the 10% EPO vehicles increased API release and diffusion when compared to the other vehicles. However, the colloidal suspension had the highest concentrations of API within the skin. Hence, all the vehicles were non-toxic and effectively delivered diclofenac through the transdermal route.

Geographical and seasonal phytochemical variation of Artemisia afra Jacq. ex Willd.

INTRODUCTION: Artemisia afra Jacq. ex. Willd. (Asteraceae) is a popular traditional medicine in South Africa, mainly used in the form of an infusion, for the treatment of respiratory ailments. Quality control methods are limited and phytochemical variation for the infusion is not well known. OBJECTIVE: To develop a sensitive quality control method for A. afra infusions by validating a liquid chromatography electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS) method and quantitatively comparing six marker compounds in A. afra samples collected from different locations and over a 12-month period. MATERIAL AND METHODS: There was a multiple reaction monitoring method optimised and validated, according to ICH and FDA guidelines, to quantify the chemical markers present in infusions. RESULTS: The chemistry differed significantly and interestingly, with an interchangeable trend between chlorogenic acid (CGA) and 4,5-dicaffeoylquinic acid (DCQA) observed in the samples collected monthly, elevated levels of CGA during winter and elevated levels of DCQA during summer. The remaining four markers showed a steady decrease as winter approached and a steady increase as summer approached. The ranges of the six markers were the following: CGA (0.68-14.68 µg/mg), DCQA (0.005-8.110 µg/mg), quercetin (0.01-0.65 µg/mg), luteolin (0.05-1.30 ng/mg), scopoletin (0.10-1.14 µg/mg), scopolin (0.03-1.21 µg/mg). CONCLUSIONS: A sensitive LC-ESI-MS/MS method was developed, validated, and used to quantify six marker compounds. The results indicated a large degree of phytochemical variation occurred across all samples tested, which highlights the importance of producing herbal medicine under controlled conditions and the necessity of analytical quality control methods.

Development and characterization of nano-emulsions and nano-emulgels for transdermal delivery of statins.

BACKGROUND: Oral administration of statins for the treatment of familial hypercholesterolemia results in poor therapeutic outcomes and patient compliance. An alternative administration route is proposed to circumvent the current limitations. This research is aimed at developing nano-emulsions and nano-emulgels as the ultimate potential delivery systems of statins for administration via the transdermal route. METHODS: Oil-in-water (o/w) nano-formulations (nano-emulsions and nano-emulgels) containing 2% (w/w) of the selected statin and 8% apricot kernel oil as oil phase were formulated. The nano-formulations were characterized using transmission electron microscopy (TEM), pH, viscosity, droplet size and zeta-potential. RESULTS: Nano-emulsions' and nano-emulgels' droplet size ranged between 114.23-169.83 nm and 149.83-267.53 nm, respectively. The addition of Carbopol® Ultrez 20 increased the nano-emulsions' viscosity (3.59-8.38 cP) resulting in the formation of nano-emulgels (viscosity: 1911.00-46,090.00 cP). The entrapment efficiency (90.77-99.55%) confirmed the incorporation of the statins. Membrane release studies indicated that statins were released at higher flux values in nano-emulsions compared to their respective nano-emulgels. Ex vivo (skin diffusion) studies indicated higher median values in the nano-emulgels compared to their nano-emulsion counterparts. CONCLUSIONS: The results indicate the benefits of nano-emulsions and nano-emulgels as potential alternative delivery systems for the transdermal delivery of statins.

Formulation of Natural Oil Nano-Emulsions for the Topical Delivery of Clofazimine, Artemisone and Decoquinate.

PURPOSE: The aim of this study was to formulate nano-emulsions comprising natural oils and the active pharmaceutical ingredients (APIs) clofazimine (CLF), artemisone (ATM) and decoquinate (DQ) in order to determine effectiveness of the nano-emulsions for topical delivery of the APIs. The APIs alone do not possess suitable physicochemical properties for topical drug delivery. METHODS: Nano-emulsions were formulated with olive and safflower oils encapsulating the APIs. Skin diffusion and tape stripping studies were performed. By using the lactate dehydrogenase (LDH) assay, in vitro toxicity studies were carried out on immortalized human keratinocytes (HaCaT) cell line to determine cytotoxicities due to the APIs and the nano-emulsions incorporating the APIs. RESULTS: The nano-emulsions were effective in delivering the APIs within the stratum corneum-epidermis and the epidermis-dermis, were non-cytotoxic towards HaCaT cell lines (p < 0.05) and inhibited Mycobacterium tuberculosis in vitro. CONCLUSION: Natural oil nano-emulsions successfully deliver CLF, ATM and DQ and in principle could be used as supplementary topical treatment of cutaneous tuberculosis (CTB). Graphical Abstract ᅟ.

Topical Delivery of Withania somnifera Crude Extracts in Niosomes and Solid Lipid Nanoparticles.

BACKGROUND: Withania somnifera is a medicinal plant native to India and is known to have anticancer properties. It has been investigated for its anti-melanoma properties, and since melanoma presents on the skin, it is prudent to probe the use of W. somnifera in topical formulations. To enhance topical drug delivery and to allow for controlled release, the use of niosomes and solid lipid nanoparticles (SLNs) as delivery vesicles were explored. OBJECTIVE: The objective of this study is to determine the stability and topical delivery of W. somnifera crude extracts encapsulated in niosomes and SLNs. MATERIALS AND METHODS: Water, ethanol, and 50% ethanol crude extracts of W. somnifera were prepared using 24 h soxhlet extraction which were each encapsulated in niosomes and SLNs. Franz cell diffusion studies were conducted with the encapsulated extracts to determine the release and skin penetration of the phytomolecules, withaferin A, and withanolide A. RESULTS: The niosome and SLN formulations had average sizes ranging from 165.9 ± 9.4 to 304.6 ± 52.4 nm with the 50% ethanol extract formulations having the largest size. A small particle size seemed to have correlated with a low encapsulation efficiency (EE) of withaferin A, but a high EE of withanolide A. There was a significant difference (P < 0.05) between the amount of withaferin A and withanolide A that were released from each of the formulations, but only the SLN formulations managed to deliver withaferin A to the stratum corneum-epidermis and epidermis-dermis layers of the skin. CONCLUSION: SLNs and niosomes were able to encapsulate crude extracts of W. somnifera and release the marker compounds, withaferin A, and withanolide A, for delivery to certain layers in the skin. SUMMARY: Withania somnifera crude extracts were prepared using ethanol, water, and 50% ethanol as solvents. These three extracts were then incorporated into niosomes and solid lipid nanoparticles (SLNs) for use in skin diffusion studies, thus resulting in six formulations (ethanol niosome, water niosome, 50% ethanol niosome, ethanol SLN, water SLN, and 50% ethanol SLN). The diffusion of two marker compounds (withaferin A and withanolide A) from the formulations into the skin was then determined. Abbreviations used: API: Active pharmaceutical ingredient, ANOVA: Analysis of variance, ED: Epidermis-dermis, HPLC: High-performance liquid chromatography, HLB: Hydrophilic-lipophilic balance, NMR: Nuclear magnetic resonance spectroscopy, PDI: Polydispersity index, SLN: Solid lipid nanoparticle, SD: Standard deviation, SCE: Stratum corneum-epidermis, TEM: Transmission electron microscopy.

In vitro wound healing and cytotoxic activity of the gel and whole-leaf materials from selected aloe species.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloe vera is one of the most important medicinal plants in the world with applications in the cosmetic industry and also in the tonic or health drink product market. Different parts of Aloe ferox and Aloe marlothii are used as traditional medicines for different applications. Although wound healing has been shown for certain aloe gel materials (e.g. A. vera ) previously, there are conflicting reports on this medicinal application of aloe leaf gel materials. AIM OF THE STUDY: The present study aimed at determining the wound healing properties of the gel and whole-leaf materials of Aloe vera, Aloe ferox and Aloe marlothii, as well as their cytotoxic effects on normal human keratinocyte cells (HaCaT). MATERIALS AND METHODS: Nuclear magnetic resonance spectroscopy was used to chemically fingerprint the aloe gel and whole-leaf materials by identifying characteristic marker molecules of aloe gel and whole-leaf materials. An MTT assay was performed to determine the cytotoxicity of the various aloe whole-leaf and gel materials on HaCaT cells. Wound healing and in vitro cell migration were investigated with HaCaT cells by means of the CytoSelect™ assay kit. RESULTS: The in vitro wound healing assay suggested that all the aloe gel and whole-leaf materials examined, exhibited faster wound healing activity than the untreated control group. After 48h, all the aloe gel and whole-leaf materials almost completely caused full wound closure, displaying 98.07% (A. marlothii whole-leaf), 98.00% (A. vera gel), 97.20% (A. marlothii gel), 96.00% (A. vera whole-leaf), 94.00% (A. ferox gel) and 81.30% (A. ferox whole-leaf) wound closure, respectively. It was noteworthy that the gel materials of all the three aloe species exhibited significantly faster (p<0.05) wound healing actions when compared to their respective whole-leaf materials at 32h. CONCLUSION: The gel and whole-leaf materials of A. vera, A. ferox and A. marlothii have shown the ability to heal wounds at a faster rate and to a larger extent than untreated keratinocytes. The MTT assay results suggested that the gel and whole-leaf materials of all the selected Aloe species showed negligible toxicity towards the HaCaT cells.

Topical delivery of roxithromycin solid-state forms entrapped in vesicles.

Recently, considerable interest developed in using newer/improved antibiotics for the treatment of Acne vulgaris. During this study, different roxithromycin solid-state forms (i.e. crystalline and amorphous) were encapsulated into vesicle systems (niosomes, proniosomes, ufosomes and pro-ufosomes) for dermis targeted delivery. Characterization of the vesicles was done with transmission electron microscopy, light microscopy, droplet size, droplet size distribution, pH, zeta-potential and entrapment efficiency percentage. Finally, comparative release and topical diffusion studies were performed, to evaluate if targeted topical delivery was obtained and if the roxithromycin solid-state amorphous forms resulted in improved topical delivery. Vesicle systems containing different roxithromycin (2%) solid-state forms were successfully prepared and characterized. The vesicles showed optimal properties for topical delivery. All carrier systems had topical delivery to the epidermis-dermis, whilst no roxithromycin was found in the receptor compartment or stratum corneum-epidermis. The niosomes were the leading formulation and the two amorphous forms had better topical delivery than the crystalline form. Successful targeted delivery of roxithromycin was obtained in the dermis, where the activity against Propionibacterium acnes is needed. The amorphous forms seemed to have held their solid-state form during formulation and in the vesicles, showing improved topical delivery in comparison to the crystalline form.

Traversing the Skin Barrier with Nano-emulsions.

BACKGROUND: In recent years, colloidal delivery systems based on nano-emulsion are gaining popularity; being used for encapsulation and delivery of many drugs. This review therefore aims at summarizing various methods of nano-emulsion formulation and their use as a topical and transdermal delivery vehicle for a number of active pharmaceutical ingredients from different pharmacological classes. METHODS: This article represents a systematic review of nano-emulsions for topical and transdermal drug delivery. A vast literature was searched and critically analysed. RESULTS: Nano-emulsions are thermokinetically stable dispersion systems, which have been used in topical and transdermal delivery of a number of pharmaceutically active compounds. Nano-emulsions have a narrow droplet size range with tuneable surface properties, which make them an ideal delivery vehicle. Nanoemulsions have a number of advantages over conventional emulsions, including easy preparation using various low and high energy methods, optical transparency, high solubilisation capacity, high stability to droplet aggregation and the ability to penetrate the skin; thus allowing the transdermal delivery of drugs. CONCLUSION: This review indicated that nano-emulsions are promising vehicle for entrapping various drugs and are suitable for traversing the skin barrier for systemic effects.

In vitro skin permeation of sinigrin from its phytosome complex.

OBJECTIVES: Sinigrin is a major glucosinolate present in plants of the Brassicaceae family. Recently, sinigrin and its phytosome formulations have been investigated for its wound-healing actions, by our research group. The aim of this study was to demonstrate sinigrin drug release from its phytosome complex and also to determine whether the phytosome complex enhances the delivery of sinigrin into the skin when compared to free sinigrin. METHODS: In vitro Franz cell diffusion studies were performed on human abdominal skin. The morphology of the phytosome complex was examined by transmission electron microscopy. The in vitro drug release was determined using dialysis sacks. KEY FINDINGS: The in vitro drug release indicated a controlled and sustained release of sinigrin from the phytosome complex. Tape stripping results showed that the sinigrin-phytosome complex (0.5155 µg/ml) statistically significantly enhanced the delivery of sinigrin into the stratum corneum-epidermis when compared to the free sinigrin (0.0730 µg/ml). CONCLUSIONS: These results suggested the possibility of utilizing sinigrin-phytosome complex, to optimally deliver sinigrin to the skin which can be further used for various skin-related diseases including wound healing.

Treatment Modalities for Acne.

Acne is a common inflammatory skin disease which affects the pilosebaceous units of the skin. It can have severe psychological effects and can leave the patient with severe skin scarring. There are four well-recognized pathological factors responsible for acne which is also the target for acne therapy. In this review, different treatment options are discussed, including topical (i.e., retinoids, and antibiotics) and systemic (i.e., retinoids, antibiotics, and hormonal) treatments. Since the general public has been showing an increasing interest in more natural and generally safer treatment options, the use of complementary and alternative medicines (CAM) for treating acne was also discussed. The use of physical therapies such as comedone extraction, cryoslush therapy, cryotherapy, electrocauterization, intralesional corticosteroids and optical treatments are also mentioned. Acne has been extensively researched with regards to the disease mechanism as well as treatment options. However, due to the increasing resistance of Propionibacterium acnes towards the available antibiotics, there is a need for new treatment methods. Additionally, the lack of necessary evidence on the efficacy of CAM therapies makes it necessary for researchers to investigate these treatment options further.

Physical stability and clinical efficacy of Crocodylus niloticus oil lotion

ABSTRACT The stability and the anti-ageing, skin hydrating and anti-erythema effects of a commercialized Crocodylus niloticus Laurenti, 1768, Crocodylidae, oil lotion was determined. The lotion was stored at controlled conditions over six months during which several stability tests were performed. For the clinical efficacy studies lotion was applied on volar forearm skin (female volunteers) and compared to a liquid paraffin-containing reference product. Skin hydrating and anti-ageing effects were determined with a Corneometer®, Cutometer® and Visioscan®, following single (3 h) and multiple applications (12 weeks). The Vapometer® and Mexameter® were utilized to determine this lotion's anti-erythema effects on sodium lauryl sulfate irritated skin. The lotion demonstrated good stability over 6 months. The reference product increased skin hydration and decreased skin wrinkles to a larger extent than the C. niloticus lotion after a single application, whereas the C. niloticus lotion decreased skin scaliness better than the reference product. During the long-term study, the reference product overall increased skin hydration more than the C. niloticus lotion, whereas C. niloticus lotion increased skin elasticity to a larger extent than the reference product. C. niloticus lotion increased skin wrinkles and decreased skin scaliness over 12 weeks. Compared to non-treated, irritated skin, C. niloticus lotion demonstrated some potential anti-inflammatory characteristics.

In vitro skin permeation of artemisone and its nano-vesicular formulations.

The artemisinin derivative artemisone has antitumor activity. In particular when encapsulated in solid lipid nanoparticles (SLNs) and niosomes, it is active against human melanoma A-375 cells, although such formulations have a negligible effect on human keratinocyte cells. The aim here was to determine whether these formulations could enhance the topical delivery and skin permeation of artemisone as a prelude to evaluating use of artemisone and related compounds for melanoma treatment. In vitro skin permeation studies were conducted to determine the concentration of artemisone delivered into the stratum corneum-epidermis and epidermis-dermis. Artemisone-SLNs delivered artemisone into the stratum corneum-epidermis at significantly higher concentration (62.632 µg/mL) than the artemisone-niosomes (12.792 µg/mL). Neither of the controls delivered artemisone into the stratum corneum-epidermis. In the epidermis-dermis, artemisone (13.404 µg/mL) was only detected after application of the SLN formulation. Overall, the excellent topical delivery of artemisone with the SLN formulation coupled with the intrinsic activity of formulated artemisone confirms potential for use in treatment of melanoma.

Essential Fatty Acids as Transdermal Penetration Enhancers.

The aim of this study was to investigate the effect of different penetration enhancers, containing essential fatty acids (EFAs), on the transdermal delivery of flurbiprofen. Evening primrose oil (EPO), vitamin F, and Pheroid technology all contain fatty acids and were compared using a cream-based formulation. This selection was to ascertain whether EFAs solely, or EFAs in a Pheroid delivery system, would have a significant increase in the transdermal delivery of a compound. Membrane release studies were performed, and the results indicated the following rank order for flurbiprofen release from the different formulations: vitamin F >> control > EPO >> Pheroid. Topical skin delivery results indicated that flurbiprofen was present in the stratum corneum-epidermis and the epidermis-dermis. The average percentage flurbiprofen diffused to the receptor phase (representing human blood) indicated that the EPO formulation showed the highest average percentage diffused. The Pheroid formulation delivered the lowest concentration with a statistical significant difference (p < 0.05) compared with the control formulation (containing 1% flurbiprofen and no penetration enhancers). The control formulation presented the highest average flux, with the EPO formulation following the closest. It could, thus, be concluded that EPO is the most favorable chemical penetration enhancer when used in this formulation.

Topical delivery of acyclovir and ketoconazole.

CONTEXT: Viral and fungal cutaneous manifestations are regularly encountered in immunocompromised human immunodeficiency virus/acquired immunodeficiency syndrome individuals and can be treated by drugs such as acyclovir and ketoconazole, respectively. OBJECTIVE: The aim of this study was to determine whether the novel Pheroid delivery system improved the transdermal delivery and/or dermal delivery of acyclovir and ketoconazole when incorporated into semi-solid formulations. MATERIALS AND METHODS: Semi-solid products (creams and emulgels) containing these drug compounds were formulated, either with or without (control) the Pheroid delivery system. The stability of the formulated semi-solid products was examined over a period of six months and included the assay of the actives, pH, viscosity, mass loss and particle size observation. Vertical Franz cell diffusion studies and tape stripping methods were used to determine the in vitro, stratum corneum (SC)-epidermis and epidermis-dermis delivery of these formulations. RESULTS AND DISCUSSION: Stability tests showed that none of the formulations were completely stable. Acyclovir showed a biphasic character during the in vitro skin diffusion studies for all the tested formulations. The Pheroid™ cream enhanced the transdermal, SC-epidermis and epidermis-dermis delivery of acyclovir the most. The average amount of ketoconazole diffused over 12 h showed improved delivery of ketoconazole, with the Pheroid™ emulgel exhibiting the best transdermal and epidermis-dermis delivery. CONCLUSION: The Pheroid formulae increased transdermal penetration as well as delivery to the dermal and epidermal skin layers. The Pheroid emulgel and the Pheroid cream increased the topical delivery of ketoconazole and acyclovir, respectively.

Stability, clinical efficacy, and antioxidant properties of Honeybush extracts in semi-solid formulations.

BACKGROUND: Honeybush extracts (Cyclopia spp.) can be incorporated into skin care products to treat conditions such as skin dryness and can function as an anti-oxidant. OBJECTIVE: To formulate Honeybush formulations and test it for antioxidant activity, skin penetration, and skin hydrating effects. MATERIALS AND METHODS: Semi-solid formulations containing either Cyclopia maculata (2%) or Cyclopia genistoides (2%) underwent accelerated stability studies. Membrane release studies, Franz cell skin diffusion and tape stripping studies were performed. Antioxidant potential was determined with the 2-thiobarbituric acid-assay and clinical efficacy studies were performed to determine the formulations' effect on skin hydration, scaliness, and smoothness after 2 weeks of treatment on the volar forearm. RESULTS: The formulations were unstable over 3 months. Membrane release, skin diffusion studies, and tape stripping showed that both formulations had inconclusive results due to extremely low concentrations mangiferin and hesperidin present in the Franz cell receptor compartments, stratum corneum-epidermis, and epidermis-dermis layers of the skin. Honeybush extracts showed antioxidant activity with concentrations above 0.6250 mg/ml when compared to the toxin; whereas mangiferin and hesperidin did not show any antioxidant activity on their own. The semisolid formulations showed the potential to emit their own antioxidant activity. Both formulations improved skin smoothness, although they did not improve skin hydration compared to the placebos. C. maculata reduced the skin scaliness to a larger extent than the placebos and C. genistoides. CONCLUSION: Honeybush formulations did not penetrate the skin but did, however, show antioxidant activity and the potential to be used to improve skin scaliness and smoothness.

Optimised transdermal delivery of pravastatin.

Wiechers' programme "Formulating for Efficacy" initiated a new strategy to optimise the oil phase of topical formulations in order to achieve optimal transdermal drug delivery. This new approach uses the "Delivery Gap Theory" on any active pharmaceutical ingredients (APIs) to test if it could enhance transdermal drug delivery. The aim of the study was to formulate six different semi-solid formulations (three creams and three emulgels) with 2% pravastatin as the API in order to investigate the "Delivery Gap Principle", by determining which formulation would deliver pravastatin best to the target-site (system circulation). The three cream- and three emulgel formulations had different polarities, i.e. a formulation with polarity equal to that of the stratum corneum (optimised), a non-polar (lipophilic)- and a polar (hydrophilic)-formulation. Franz cell diffusion studies were executed over 12h and the optimised emulgel (2.578µg/cm(2)) had the highest median amount per area obtained. Tape stripping followed the diffusion studies and in the stratum corneum-epidermis, the hydrophilic emulgel (1.448µg/ml) contained the highest median pravastatin concentration and the epidermis-dermis the optimised emulgel (0.849µg/ml) depicted the highest pravastatin concentration. During this study, it was observed that when both emulgel and cream formulations were compared; the emulgels enhanced the delivery of pravastatin more than the creams.

Penetration enhancing effects of selected natural oils utilized in topical dosage forms.

CONTEXT: Various natural products, including oils, have been utilized as penetration enhancers due to their "safety profiles". These oils contain fatty acids promoting skin permeability through lipid fluidization within the stratum corneum; and might therefore be able to effectively enhance transdermal drug delivery. OBJECTIVE: We investigated possible penetration enhancing properties of selected oils, utilizing flurbiprofen as marker compound in emulgel formulations. The formulations were compared to a liquid paraffin emulgel and a hydrogel to establish any significant penetration enhancing effects. METHODS: Gas chromatographic analysis of the natural oils was performed at ambient temperature to determine the fatty acid composition in each selected natural oils. Franz cell diffusion studies and tape stripping methods were employed to study delivery of the marker into, and through the skin. RESULTS: The following rank order for the emulgel flux-values was obtained: Hydrogel >>>> olive oil >> liquid paraffin >> coconut oil > grape seed oil >> Avocado oil ≥ Crocodile oil >> Emu oil. DISCUSSION: Results suggested that oils containing predominantly mono-unsaturated oleic acid, on average increased the flux of the marker to a larger extent than oils containing an almost even mixture of both mono- and poly-unsaturated fatty acids. Oils comprising saturated fatty acids (SFAs) with alkyl chains between C12 and C14, increased the marker flux to a higher extent than oils containing C16-C18 SFAs. Effects observed for branched fatty acids, however, did not vary significantly from effects for unbranched fatty acids with the same carbon chain length. CONCLUSION: Natural oils possess penetration enhancing effects.

Topical Delivery of 5-Fluorouracil from Pheroid™ Formulations and the In Vitro Efficacy Against Human Melanoma.

Drug delivery vehicles can influence the topical delivery and the efficacy of an active pharmaceutical ingredient (API). In this study, the influence of Pheroid™ technology, which is a unique colloidal drug delivery system, on the skin permeation and antimelanoma efficacy of 5-fluorouracil were investigated. Lotions containing Pheroid™ with different concentrations of 5-fluorouracil were formulated then used in Franz cell skin diffusion studies and tape stripping. The in vitro efficacy of 5-fluorouracil against human melanoma cells (A375) was investigated using a flow cytometric apoptosis assay. Statistically significant concentrations of 5-fluorouracil diffused into and through the skin with Pheroid™ formulations resulting in an enhanced in vitro skin permeation from the 4.0% 5-fluorouracil lotion (p < 0.05). The stratum corneum-epidermis and epidermis-dermis retained 5-fluorouracil concentrations of 2.31 and 6.69 µg/ml, respectively, after a diffusion study with the 4.0% Pheroid™ lotion. Subsequent to the apoptosis assay, significant differences were observed between the effect of 13.33 µg/ml 5-fluorouracil in Pheroid™ lotion and the effects of the controls. The results obtained suggest that the Pheroid™ drug delivery system possibly enhances the flux and delivery of 5-fluorouracil into the skin. Therefore, using Pheroid™ could possibly be advantageous with respect to topical delivery of 5-fluorouracil.