Transdermal Permeation Studies Research Articles

Umbilical therapy for promoting transdermal delivery of topical formulations: Enhanced effect and underlying mechanism

Umbilical paste therapy is a promising method to promote transdermal drug delivery of topical formulations. This work investigated the effect and mechanism of transdermal drug delivery through the umbilical skin. The transdermal permeation studies showed the phenomenon of higher cumulative penetration and faster penetration rates for drug through the umbilical skin compared with non-umbilical skin, namely umbilical pro-permeability. This special transdermal permeability of drugs is influenced by their molecular weight, logP value, ability to form hydrogen bonds, and molecular volume. The underlying mechanism of umbilical pro-permeability was elucidated from unique structure and regulation the effect of drugs on microcirculation in the umbilical skin. Mechanistic studies revealed that this phenomenon was not only associated with the structural and physiological properties of the skin but also to the interactions between drugs and different skin layers. The umbilical pro-permeation is attributed to the thinner stratum corneum layer, differences in stratum corneum lipid composition and keratin structure, and lower levels of intercellular tight junction proteins in the viable epidermis and dermis layer of the skin. Our research indicated that umbilical paste therapy enhanced the transdermal delivery and absorption of drugs by stimulating local blood flow through mast cell activation. Surprisingly, skin temperature modulation and calcitonin gene-related peptide and substance P levels did not appear to significantly affect this process. In conclusion, umbilical drug administration, as a straightforward and non-invasive approach to enhance transdermal drug delivery, presents novel concepts for continued investigation and practical implementation of transdermal drug delivery systems.

Innovative insight into the mechanism of enantioselective skin permeation for chiral drugs

ABSTRACT Objectives A profound comprehension of the molecular mechanisms underpinning the enantioselective transdermal permeation of chiral drugs is critical in the design and assessment of transdermal preparations. The primary objective of this study is to investigate the distinct skin permeation behaviors exhibited by enantiomers of non-steroidal anti-inflammatory drugs (NSAIDs) and elucidate the intricate molecular mechanism at play. Methods In vitro and in vivo transdermal permeation studies of chiral NSAIDs were performed using transdermal patch and solution system. Chiral interaction between NSAIDs enantiomers and synthesized chiral ceramide present in the skin was characterized to clarify the different transdermal behaviors. Results The S-enantiomers of NSAIDs exhibited higher permeability through the skin than R-enantiomer in vitro (1.5-fold) and in vivo (2.0-fold), which was attributed to a stronger interaction between S-enantiomer and ceramide caused by more favorable spatial conformations. S-enantiomer required lower activation energy (24.4 kJ/mol) and Gibbs energy (43.3 kJ/mol), which was favorable in forming the H-bond with ceramide in the skin, resulting in more permeation. Conclusion This research furnished an innovative comprehension of the molecular underpinnings governing the enantioselective permeation of drug enantiomers through the skin, fostering the minimization of undesired enantiomer ingestion (distomers) and amplifying therapeutic efficiency.

Zn/Al Layered double hydroxides nanostructure as effective controlled release vehicle of nicotinic acid for topical applications

The delivery of active ingredients through the human skin is an arduous exercise because of its structural intricacy and outstanding barrier characteristics. Nanotechnological developments have produced advanced delivery systems based on nanomaterials to reinforce the skin's ability to absorb hydrophobic, hydrophilic active ingredients and macromolecules. In this study, inorganic crystalline layered double hydroxides nanostructures (LDH) were used as an advanced release system for nicotinic acid, with skin lightening properties. Nicotinic acid was incorporated into the interlayer space of Zn/Al LDH, by co-precipitation method to develop LDH hybrids. The LDH hybrids were characterized using FTIR, XRD, TGA, and SEM. Intercalation of nicotinic acid in the interlayer space of Zn/Al LDH was ascertained by the shifting of the basal spacing d (003) reflection in the XRD pattern, to lower angles (2θ). FTIR spectra of the Zn/Al LDH hybrids displayed the absorption frequencies of nicotinic acid that indicated the presence of nicotinic acid within the LDH matrix. TGA showed that nicotinic acid intercalated in the interlayer of LDH exhibited better thermal stability than the free form of nicotinic acid. In vitro release experiments revealed controlled and pH-responsive release of nicotinic acid from Zn/Al LDH. Transdermal permeation studies employing Franz- diffusion cells demonstrated that the formulation containing nicotinic acid-intercalated Zn/Al LDH considerably enhanced the penetration of nicotinic acid compared to the formulation containing the free form of nicotinic acid. Thus, Zn/Al LDH has great potential for use as a sustained and controlled release reservoir of nicotinic acid in skin care and other topical applications.

Novel tip-loaded dissolving and implantable microneedle array patches for sustained release of finasteride

Finasteride (FND) is a competitive inhibitor of 5α-reductase, an enzyme involved in benign prostatic hyperplasia (BPH) and androgenic alopecia. FND is administered in oral, often lifelong treatments, increasing the pill burden of polymedicated patients. Microneedle array patches (MAPs) are minimally invasive devices that painlessly pierce the outermost layers of the skin, forming slowly-dissolving drug depots in the dermis, which can release drugs over weeks or months, making this platform an attractive, patient-friendly option for long-term treatments. This work describes the development of long-acting dissolving and implantable PLGA MAPs aimed for systemic release of FND for at least two weeks. Mechanically strong tip-loaded MAPs with pyramidal geometry were obtained using micromoulding methodology. In vitro studies revealed that the dissolving and implantable MAPs were able to release the drug for over 7 and 14 days, respectively. Skin deposition experiments in Franz cells demonstrated that after 24 h, dissolving and implantable MAPs were able to deposit 629.00 ± 214.54 μg and 1861.64 ± 383.30 μg of FND in the skin, respectively. On the other hand, transdermal permeation studies showed that both formulations produced a slow release of the drug to the receptor compartment of the Franz cells, with dissolving and implantable MAPs releasing 90.43 ± 6.20 μg and 27.80 ± 3.94 μg of FND after 24 h. The formulations described here could be an alternative to current oral treatments, having the potential to deliver the drug for extended periods, simplifying the treatment of BPH and androgenic alopecia.

HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC ESTIMATION METHOD FOR TRANSDERMAL DIFFUSION STUDY OF GRANISETRON

Objective: The study is aimed to develop a simple, isocratic and sensitive reversed-phase high-performance liquid chromatography method for the analysis of granisetron during transdermal permeation studies through porcine ear epithelium.
 Methods: A reversed-phase (C18) column was used with ultraviolet detection at 210 nm. Selected mobile phase contained 25% (v/v) of acetonitrile and 75% (v/v) of 0.25 mM potassium dihydrogen orthophosphate solution pH adjusted to 3.0 using 1% orthophosphoric acid solution.
 Results: Calibration curve showed good linearity over 0.1–30 μg/mL concentration range of porcine ear permeates in 80% ethanol and 20% water (blank permeates). The applicability of the method was demonstrated by the analysis of diffusion study samples of granisetron through porcine ear epithelium and the steady-state permeability flux (J) from ethanolic solution was found to be 4.707 µg/square cm/h.
 Conclusion: The developed method can be used in the analysis of diffusion study samples of granisetron transdermal formulations through the porcine ear epithelium.

A bilayer microneedle for therapeutic peptide delivery towards the treatment of diabetes in db/db mice

Microneedles (MN) provide an alternative approach to hypodermic injection for the delivery of biomacromolecule in a minimally invasive manner. In this work, lixisenatide-loaded bilayer MNs were prepared using polyvinylpyrrolidone K29/32 (PVP K29/32) as the matrix material via a two-step molding method to avoid therapeutic wastes in the base layer. The MNs obtained in our study displayed good shapes and sufficient mechanical strength. After insertion into the rat skin, the needles of MNs fully dissolved in less than 3 min to release the therapeutic payloads. The Franz cell based transdermal permeation study revealed that the MNs could dramatically promote transdermal permeation efficiencies of the water-soluble rhodamine B and FITC-dextran (5 kDa). The skin insertion of MNs caused slight irritation and the skin recovered shortly. Also, the PVP K29/32-based MNs displayed minimum cytotoxicity against HaCaT cells and murine L929 cells. The in vivo pharmacodynamic study in db/db mice demonstrated that the MNs successfully delivered Lix and downregulated the blood glucose levels. Overall, the PVP K29/32-based bilayer fast-dissolving MNs offer a unique transdermal delivery system which can be further explored to a variety of biological therapeutics.

Formulation and Evaluation of Ondansetron HCl Nanoparticles for Transdermal Delivery

Ondansetron HCl (OND) is a potent antiemetic drug used for control of nausea and vomiting associated with cancer chemotherapy. It exhibits only 60 – 70 % of oral bioavailability due to first pass metabolism and has a relative short half-life of 3-5 hours. Poor bioavailability not only leads to the frequent dosing but also shows very poor patient adherence. Hence, in the present study an approach has been made to develop OND nanoparticles using eudragit® RS100 and eudragit® RL100 polymer to control release of OND for transdermal delivery and to improve patient compliance.
 Six formulas of OND nanoparticles were prepared using nanoprecipitation technique. The particles sizes and zeta potential were measured using zeta-plus analyzer. The particle morphology was also studied using scanning electron microscopy (SEM). The in-vitro release of the drug from the nanoparticles was carried out in phosphate buffer saline pH 7.4.
 The particle size of the prepared NPs were in nano size which ranged from (95.34 to 275.84 nm) with positive zeta potential. The drug entrapment efficiency was varied with the drug polymer ratio from 41.87% to 78.45%. The SEM showed uniform shape and regularly distributed particle sizes. The in-vitro drug release study exhibited the sustained release of OND with burst release. The cumulative percentage released after 12 hr. were between were 77.89 and 96.01%.
 Also the transdermal permeation study show that nanoparticles permeate more efficiently than aqueous solution of the drug through the skin by approximately two fold. OND nanoparticles were prepared successfully using nanoprecipitation method. The controlled drug release aimed for transdermal drug delivery could be obtained by using eudragit RS100 and eudragit RL100 polymers which can reduce dosing frequency, decrease side effects and improve patient compliance.

Deferiprone Stimulates Aged Dermal Fibroblasts via HIF-1α Modulation.

Hypoxia-inducible factor 1α (HIF-1α), a transcription factor responsible for tissue homeostasis and regeneration, presents reduced functionality in advanced age. In addition to absence of oxygen, sequestration of iron also stimulates HIF-1α. Therefore, we analyzed the efficacy of the iron-chelator deferiprone (DFP) at stimulating dermal fibroblasts. The main objective of this study was to quantify the DFP concentrations capable of stimulating dermal fibroblasts in vitro and to correlate the effective DFP concentrations with the ability of DFP to penetrate the epidermis, reach the dermis, and activate HIF-1α in vivo. We measured cell proliferation, metabolic activity, HIF-1α expression, and lactate dehydrogenase levels of both young and aged fibroblasts after a 24-hour in vitro preconditioning with DFP. In addition, we evaluated cell survival rates and morphology with different cellular stainings. Finally, we performed a transdermal permeation study with a 1% DFP topical formulation to quantify the concentration required to reach the dermis. In vitro administration of iron-chelation therapy (156-312.5 µg/mL DFP ) on aged fibroblasts resulted in activation of various antiaging processes. The concentration required to reach the dermis within 24 hours was 1.5% (0.15 mg/mL), which corresponds well with the effective doses of our laboratory analyses. The activation of HIF-1α by DFP enhances cell metabolism, proliferation, and survival of fibroblasts while reducing lactate dehydrogenase levels. Modulation of HIF-1α is linked to activation of key regeneration enzymes and proteins, and by proxy, antiaging. Therefore, the antiaging properties of DFP and its satisfactory dermal penetration make it a promising regenerative agent.

Anti-aging formulation of rosmarinic acid-loaded ethosomes and liposomes

The study was aimed to evaluate the effectiveness of rosmarinic acid (RA) loaded ethosomes (ETHs) and liposomes (LPs) when subjected to the transdermal application. RA-loaded ETHs and LPs were prepared, optimised, and characterised. The ex vivo permeation studies of formulations using mouse abdominal skin were performed. Antioxidant activities and the inhibitory effects of formulations on collagenase and elastase enzymes were measured. Optimised ethosomal formulation (F3) was showed nanometric size range (138 ± 1.11 nm) and greatest entrapment (55 ± 1.80%), was selected for further transdermal permeation studies. Skin permeation profile of the nanoformulations analysed by HPLC revealed an enhanced permeation of ETHs. Transdermal flux of ETHs was found to be higher than RA solution and LPs. Enzyme inhibitions of ETHs were the significant difference found between ETHs and LPs (p < 0.05). ETHs were found to be more effective and successful than LPs. Results suggest that ETHs are more effective than LPs for transdermal delivery of RA.

Hyaluronic acid based nanocrystals hydrogels for enhanced topical delivery of drug: A case study

The objective of this study is to use a carbohydrate polymer hyaluronic acid (HLA) as matrix to design novel transdermal nanogel loading poorly soluble drug nanocrystals. Baicalin nanocrystals (BCA-NC) were prepared by coupling homogenization technology and spray-drying technology. The morphology, the rheological behavior and transdermal permeation studies of HLA based BCA-NC-gel were evaluated. The results demonstrated that the BCA-NC could be successfully prepared in terms of trehalose after spray-drying. The trehalose could prevent the aggregation of BCA-NC during spray-drying. It was discovered that, the BCA-NC-gel with 1% HLA possessed the favorable gelatin capacity and thinning shear rheological property. In vitro transdermal permeation studies of BCA-NC-gel/HLA studies indicated a marked increase in the skin permeation of BCA. And the transdermal flux of BCA-NC-gel with 1% HLA were 20.65-fold higher (p < 0.01) than that of coarse BCA-gel, which could be attributed to particles size reduction of BCA-NC and bioadhesive property of HLA. And the morphology characterization of BCA-NC-gel/HLA demonstrated that BCA-NC could be imprisoned into the gel network of HLA, which might prevent it from aggregation in gel. In conclusion, HLA based nanogel system is a promising carrier for effectively transdermal delivery of poorly soluble drug.

Microneedle-Mediated Transdermal Delivery of Bevacizumab.

Bevacizumab is a recombinant humanized monoclonal antibody used clinically as a combination chemotherapeutic. Antibody therapeutics are usually formulated as parenteral injections, owing to their low oral bioavailability. Microneedle technology provides a transdermal alternative for drug-delivery using micron-scale needle structures to penetrate directly through the stratum corneum into the dermal interstitium. This study describes the design, formulation, and in vitro characterization of both dissolving and hydrogel-forming microneedle array platforms for transdermal delivery of bevacizumab. Bevacizumab recovery and transdermal permeation studies were conducted and analyzed using bevacizumab specific ELISA. Prototype microneedle-patches were tested in vivo in Sprague-Dawley rats with serum, exterior lumbar and axial lymph nodes, spleen, and skin tissue concentrations of bevacizumab reported. This work represents the first example of high dose transdermal delivery of an antibody therapeutic in vivo using dissolving and hydrogel-forming microneedle platforms. Basic pharmacokinetic parameters are described including hydrogel-forming microneedles: Cmax 358.2 ± 100.4 ng/mL, Tmax 48 h, AUC 44357 ± 4540, and Css 942 ± 95 ng/mL, highlighting the potential for these devices to provide sustained delivery of antibody therapeutics to the lymph and systemic circulation. Targeted delivery of chemotherapeutic agents to the lymphatic system by MN technology may provide new treatment options for cancer metastases.

Transdermal permeation of Zanthoxylum bungeanum essential oil on TCM components with different lipophilicity

ObjectiveTo investigate the percutaneous penetration enhancement effect of essential oil from Zanthoxylum bungeanum Maxim. (Z. bungeanum oil) on active components in externally-applied traditional Chinese medicines. MethodsFive model drugs, geniposide, puerarin, ferulic acid, tetramethylpyrazine, and osthole, were chosen based on their lipophilicity and tested using in vitro transdermal permeation studies consisting of Franz diffusion cells and full thickness rat abdominal skin. Scanning electron microscopy was employed to observe the morphological changes of rat skin tissue after treatment with Z. bungeanum oil. The molecular interactions between the oil and the polar head groups in stratum corneum (SC) lipids were monitored using molecular dynamic simulation, and the SC/vehicle partition coefficients and saturation solubilities of the selected model drugs treated with and without the oil were also determined to ascertain its mechanisms of action. ResultsAs oil concentration increased, the log ERflow trended toward a negative linear relationship with the lipophilicity of drugs. After treatment with Z. bungeanum oil, a mild lifting up and wrinkle on the SC surface were observed, and appeared to become more pronounced as oil concentration increased. There was no significant difference between the control and the Z. bungeanum oil at different concentrations in terms of saturation solubility of GP, while saturation solubilities of the 4 other drugs gradually increased as oil concentration increased. The oxygen-containing constituents in Z. bungeanum oil, such as terpinen-4-ol and 1,8-cineole, which accounted for 57.95% of total oil, could form stable hydrogen bonds with the polar head group of ceramide 3. ConclusionZ. bungeanum oil facilitated transdermal permeation of drugs with different lipophilicity, including the extremely hydrophilic and lipophilic drugs, whereas it exhibited greater enhancement activity for strongly hydrophilic drugs. The mechanisms of transdermal permeation enhancement by the oil could be explained with SC/vehicle partition coefficient, saturation solubility, and the interactions with SC lipids.

A UHPLC-UV Method to Quantify Skin Deposition and Transdermal Permeation of Tizanidine Hydrochloride.

Tizanidine hydrochloride is an α2-adrenergic agonist used for the symptomatic relief of spasticity associated with multiple sclerosis or with spinal cord injury or disease. The objective of this study was to develop an isocratic, robust and sensitive ultra-high performance liquid chromatography method using UV detection for use in a project to develop a transdermal therapeutic system to deliver tizanidine across the skin. Isocratic separation was achieved using a C18 column and a mobile phase comprising a 80:20 mixture of 0.004% trifluoroacetic acid in water and MeCN (pH* 3.2) at a flow rate of 0.2 mL min(-1) Tizanidine eluted at 1.499 min and the total run time was 2 min. The method was specific, robust and the response was accurate, precise and linear from 17.4 to 290 ng mL(-1) In contrast to existing methods, the method developed here was validated over a concentration range so as to include the low concentrations frequently observed in transdermal permeation studies and in samples extracted from the cutaneous matrix. Its suitability for use in transdermal permeation studies was subsequently tested and confirmed in preliminary experiments using porcine skin in vitro.

Temperature influencing permeation pattern of alfuzosin: An investigation using DoE

Background and objectiveThere has been relatively little investigation of the effect of temperature on skin permeation compared to other methods of penetration enhancement. A principal physicochemical factor which controls the passive diffusion of a solute from a vehicle into the skin arises from the skin temperature. The aim of this ex vivo study was to probe into the effect of heat on transdermal absorption of alfuzosin hydrochloride from ethyl cellulose-polyvinyl pyrrolidone (EC-PVP) based transdermal systems. Materials and methodsPrinciples of design of experiment (DoE) were used to systematically study the influence of temperature on transdermal permeation of alfuzosin. Ex vivo transdermal permeation studies were carried out at varied donor compartment temperatures. Permeation data analysis was carried out and activation energy for transdermal permeation was estimated. ResultsTemperature found to enhance ex vivo permeation parameters of alfuzosin hydrochloride from its transdermal systems. It was also noted that chemical permeation enhancers potentiate permeation enhancing effect of temperature. The permeation flux values approximately doubled after exposure to 45°C. The activation energy for transdermal permeation was found lower for the runs with chemical permeation enhancers indicating existence of a lower energy barrier in the presence of chemical permeation enhancers. ConclusionThe method reported here is a simple and useful tool for studying the effect of heat on percutaneous absorption. Such temperature dependent enhancement of flux can be more pronounced at skin surface temperatures >45°C.

An Explanation for the Difference in the Percutaneous Penetration Behavior of Tamsulosin Induced by Two Different O-Acylmenthol Derivatives

Using tamsulosin (TAL) as a model drug, the aim of this study was to investigate and compare the percutaneous permeation behavior of two menthol derivatives, 2-isopropyl-5-methylcyclohexyl heptanoate (M-HEP) and 2-isopropyl-5-methylcyclohexyl decanoate (M-DEC). In vitro transdermal permeation study was carried out using porcine skin. The residual amount of enhancers in the skin after permeation experiment was determined by gas chromatographic (GC) method. The penetration depths of fluorescein were visualized by two-photon confocal laser scanning microscopy (2P-LSM) after the skin being treated with different enhancers. Furthermore, changes in the stretching frequency of functional group of ceramide were investigated by using attenuated total reflectance Fourier transform infrared (ATR-FTIR) technique. After M-HEP addition, the cumulative amount of TAL permeated in 8 h (Q8) reached 20.57±0.54 μg/cm2 and the depth of fluorescein was 40 μm; the CH2 of ceramide symmetric stretching frequency was 4 cm−1 blue shifted. However, M-DEC has an opposite effect on TAL permeation compared with that of M-HEP. TAL is a crucial factor affecting permeation procedure, and microenvironment of lipid region determines promotion capability of the enhancers.

Diffusion Behaviors of Fluorescence Probe Molecules Through the Stratum Corneum Layer Under Physical Stress

This study experimentally demonstrates how application of an external physical stress onto the skin membrane affects the permeation of penetrating molecules. As a proxy of active compounds, in this study, a series of fluorescence probe molecules were utilized. We observed that skin permeation could be enhanced by imparting vertical strokes from a tapping head consisting of projections onto the skin. This was confirmed with consistency from in vitro and in vivo transdermal permeation studies. After an effective physical stress was applied to the skin, the permeation depth of probe molecules remarkably increased, which was comparable to the case of topical treatment. This seems to arise from temporal disordering of the stratum corneum layer in response to the applied physical stress.

In vivo microdialysis for the evaluation of transfersomes as a novel transdermal delivery vehicle for cinnamic acid

In this study, cinnamic acid-loaded transfersomes were prepared and dermal microdialysis sampling was used in Sprague–Dawley rats to compare the amount of drug released into the skin using transfersomes as transdermal carriers with that released on using conventional liposomes. The formulation of cinnamic acid-loaded transfersomes was optimized by a uniform design through in vitro transdermal permeation studies. Hydration time was confirmed as a significant factor influencing the entrapment efficiency of transfersomes, further affecting their transdermal flux in vitro. The fluxes of cinnamic acid from transfersomes were all higher than those from conventional liposomes, and the flux from the optimal transfersome formulation was 3.01-fold higher than that from the conventional liposomes (p < 0.05). An in vivo microdialysis sampling method revealed that the dermal drug concentrations from transfersomes applied on various skin regions were much lower than those required with conventional liposomes. After the administration of drug-containing transfersomes and liposomes on abdominal skin regions of rats for a period of 10 h, the Cmax of cinnamic acid from the compared liposomes was 3.21 ± 0.25 μg/mL and that from the transfersomes was merely 0.59 ± 0.02 μg/mL. The results suggest that transfersomes can be used as carriers to enhance the transdermal delivery of cinnamic acid, and that these vehicles may penetrate the skin in the complete form, given their significant deformability.

탄성 리포좀을 사용한 쿼세틴의 경피 전달: 제조, 특성 그리고 In Vitro 피부 투과 연구

본 연구에서는 일반 리포좀의 단점을 보완하기 위하여 인지질(PC)과 계면활성제(<TEX>$Tego^{(R)}$</TEX> care 450)로 구성된 탄성 리포좀을 제조하였다. 탄성 리포좀의 유효성분으로 천연 항산화제로 알려진 쿼세틴을 담지하였고, 탄성 리포좀의 입자크기 및 가변형성과 쿼세틴의 포집 효율, 안정성, in vitro 피부투과를 평가하였다. 쿼세틴을 담지한 탄성 리포좀의 평균 입자크기는 208.2~303.4 nm이였고, 포집효율은 64.1~87.5%로 측정되었다. 0.1% 쿼세틴을 담지한 탄성리포좀 중에서 인지질과 계면활성제 비율이 90 : 10인 경우가 가장 높은 포집효율(87.5%)과 가변형성 지수(28.3)를 나타내었다. 이 제형을 대상으로 피부 투과 실험을 진행하였다. 그 결과 대조군으로 사용된 일반 리포좀(<TEX>$114.8{\mu}g/cm^2$</TEX>)과 1,3-butylene glycol(<TEX>$75.1{\mu}g/cm^2$</TEX>) 용액보다 탄성 리포좀의 피부 투과능(<TEX>$164.6{\mu}g/cm^2$</TEX>)이 훨씬 더 크게 나타났다. 이러한 결과들로 미루어 보아 <TEX>$Tego^{(R)}$</TEX> care 450을 이용한 탄성 리포좀이 피부를 통한 유효성분 전달에 유용하게 이용될 수 있음을 확인하였다. In this study, the elastic liposome consisted of egg phospholipids and edge activator (<TEX>$Tego^{(R)}$</TEX> care 450) was prepared in order to supplement the defect of the conventional liposome. We prepared elastic liposome containing quercetin, known as natural antioxidant, and evaluated the vesicles size, elasticity, loading efficiency, stability, and in vitro skin permeation. The mean diameter of quercetin loaded elastic liposome formulations ranged between 208.2~303.4 nm and loading efficiency was observed 64.1~87.5%. The highest loading efficiency (87.5%) and deformability (28.3) were observed at the optimal ratio of 90 : 10 (egg phospholipids : <TEX>$Tego^{(R)}$</TEX> care 450) among 0.1% quercetin loaded elastic liposome formulations. The elastic liposome formulation was selected for further transdermal permeation study. The elastic liposome (<TEX>$129.9{\mu}g/cm^2$</TEX>) exhibited more skin permeability than general liposome (<TEX>$114.8{\mu}g/cm^2$</TEX>) and 1,3-butylene glycol (<TEX>$75.1{\mu}g/cm^2$</TEX>) solution. This results suggest that the elastic liposome formulation using <TEX>$Tego^{(R)}$</TEX> care 450 as a major edge activator could be useful for the delivery of active ingredient through the skin transdermal.

Mechanism of Nanoparticle Formation from Ternary Coground Phenytoin and Its Derivatives

The mechanism of drug nanoparticle formation of phenytoin (DPH) and its derivatives monomethylphenytoin (MDPH) and dimethylphenytoin (DMDPH) was investigated. The drug, polyvinylpyrrolidone K17 (PVP), and sodium dodecyl sulfate were coground to obtain the ground mixture (GM). The DPH GM was amorphous; however, MDPH and DMDPH GMs contained drug crystals. Spectral changes in infrared and (13)C solid-state nuclear magnetic resonance were observed in the DPH GM, partially observed in the MDPH GM, and hardly observed in the DMDPH GM. Mean particle sizes of the DPH, MDPH, and DMDPH GM nanosuspension were almost the same; however, stability after storage differed in the order of DPH > MDPH > DMDPH. The intermolecular interaction between the drug and PVP reflected not only the crystallinity of the drug in the GM but also the stability of the GM suspension. The size and stiffness of drug nanoparticles were evaluated using atomic force microscopy. Crystallization of the amorphous GM and agglomeration of the primary nanocrystals were observed in the DPH GM suspension. In contrast, primary nanocrystals were observed in the DMDPH GM suspension. The size of the drug nanocrystals formed from the different molecular states of the drug in the GM reflects the agglomerated states in water and stability.

Preparation of a ligustrazine ethosome patch and its evaluation in vitro and in vivo

BackgroundThe purpose of this study was to develop a transdermal ligustrazine patch containing a stable formulation and with good entrapment efficiency, release rate, and transdermal absorption.MethodsLigustrazine ethosomes were prepared by ethanol injection-sonication, with entrapment efficiency as an indicator. Using acrylic resin as the primary constituent, the ligustrazine ethosome patch was prepared by adding succinic acid as a crosslinking agent and triethyl citrate as a plasticizer. In vitro release and transdermal permeation studies were carried out. Finally, a pharmacokinetic study was carried out in rats to explore relative bioavailability. The formulations of ligustrazine ethosome were 1% (w/v) phospholipid, 0.4% (w/v) cholesterol, and 45% (v/v) ethanol.ResultsLigustrazine ethosomes were obtained with an average particle size of 78.71 ± 1.23 nm and an average entrapment efficiency of 86.42% ± 1.50%. In vitro transdermal testing of the ligustrazine ethosome patches showed that the cumulative 24-hour amount of ligustrazine was up to 183 ± 18 μg/cm2. The pharmacokinetic results revealed that the relative bioavailability was 209.45%.ConclusionCompared with conventional ligustrazine administration, ligustrazine ethosome patches could promote better drug absorption and increase bioavailability. This study demonstrates that the transdermal action of the ligustrazine ethosome patch was comparatively good.