Adapalene Research Articles

Multi-drug hybrid delivery systems with distinct release profiles based on gelatin/collagen containing vesicles derived from block copolymers

Hybrid delivery systems can release multiple drugs with different profiles and have several applications, including skin dressing. In this work, the co-solvent technique was used for the preparation of nanometric vesicles based on poly(styrene-b-ethylene oxide) block copolymer (BCPVs) containing adapalene (AD). The BCPVs were incorporated into collagen and gelatin matrices together with free AD and silver sulfadiazine (SSD). The AD content of BCPVs and their release capacity were analyzed by using ultraviolet-visible spectroscopy (UV–Vis). The gelatin and collagen matrices were evaluated for their ability to release AD and SSD through an in vitro release study. The obtained results confirmed that the production of empty and AD-loaded BCPVs was viable. The degree of AD encapsulation in BCPVs was 9.0% and the in vitro test revealed a constant, slow, and prolonged release of AD content from AD-loaded BCPVs. The combination of free and encapsulated multiple drugs in hybrid delivery systems based on gelatin and collagen matrices was shown to act as a skin dressing that combined the progressive release of large amounts of drugs within the first hours of use (to restrict infection) with a more prolonged and slow release of AD to enhance skin healing.

Optimization of nanostructured lipid carriers loaded with retinoids by central composite design

The aim of this study was to design and optimize a new formulation of lipid nanoparticles for the topical administration of retinoids. The standard procedure involves nanostructured lipid carriers (NLCs) synthesized by the miniemulsion methodology, using sunflower oil as a bioactive ingredient and retinyl palmitate (RP) as model retinoid.A 5-factor, 3-level central composite design was used to predict responses and construct 3D-response contour plots. The independent variables were the concentration of total lipids, solid lipid, surfactant, encapsulated retinoid and number of carbons on the solid lipid fatty acid chain length, in function of the selected responses as the particle size, surface charge of the nanoparticles and the encapsulation efficiency (EE %) at 3 levels. Experimental trials were performed at all 31 possible combinations.An optimized NLC composition of 2.5% total lipids, 2.0% myristic acid and 0.5% sunflower oil and 1.5% of surfactant Tween 80 was reached. The type of surfactant was adjusted from Tween 80 to Span 80 to improve the electrostatic stability of the lipid nanoparticles and the resultant optimized NLC formulation was evaluated to incorporate another two retinoids as tretinoin (TRT) and adapalene (ADP).The resultant retinoid delivery systems were characterized in terms of particle size and electrostatic stability, morphology, crystallinity of the lipid matrix, EE (%) and drug loading capacity and release profile. Particle sizes of 134.5 ± 5.4 nm and zeta potential values of −57.0 ± 2.8 mV were obtained for optimized ADP-NLCs and high entrapment efficiency values were obtained for RP-NLC, TRT-NLC and ADP-NLC as 84.4 ± 3.0%, 84.1 ± 7.8% and 73.7 ± 3.3%, respectively. DSC analysis indicated that the melting temperatures of the three optimized NLCs loaded with the retinoids were above 40 °C, proving to be suitable for use in topical administration. The in vitro drug release studies were conducted for 48 h, using a dialysis regenerated cellulose membrane. The results demonstrated a very well-controlled release of RP and TRT, which improves the stability of these active compounds and confirms a high encapsulation efficiency.

The effectiveness of adapalene 0.1% with intense pulsed light versus benzoyl peroxide 5% with intense pulsed light in the treatment of acne vulgaris: A comparative study.

Background:Acne vulgaris (AV) is one of the most common skin diseases with major psychological impacts. Hence, selecting the best treatment modality is so important; there are different ways to treat AV such as topical and systemic agents, laser, and also photodynamic therapy. In this study, we tried to assess the difference between the efficacy of combination therapy with intense pulsed light (IPL) and benzoyl peroxide (BPO) in comparison with IPL and adapalene (AD) in the treatment of the mild to moderate AV.Materials and Methods:Thirty Iranian females in reproductive age with mild to moderate acne were enrolled in this study. The left and right side of the patients were randomized to receive either AD 0.1% or BPO 5% every other day plus three sessions of monthly apart IPL in the treatment of AV. Different parameters of AV such as acne severity index (ASI), total acne lesions counting (TLC), and Acne Global Severity Scale (AGSS) were measured before, during, and after the treatments.Results:There was a significant difference regarding AGSS, TLC, and ASI before and after treatment with AD plus IPL (P < 0.001). Furthermore, there was a significant difference regarding AGSS, TLC, and ASI before and after treatment with BP plus IPL (P < 0.001). However, no significant difference regarding AGSS, TLC, and ASI were observed between the 2 groups after treatment (P > 0.05). No significant side effects were observed in both groups.Conclusion:Our study shows that there was not any significant difference between combining IPL with either AD or BPO so we can use either one of these combinations to achieve similar efficacy.

Efficacy and safety of 2% supramolecular salicylic acid compared with 5% benzoyl peroxide/0.1% adapalene in the acne treatment: a randomized, split-face, open-label, single-center study

Background Topical drugs for mild to moderate acne include adapalene (ADA) and benzoyl peroxide(BPO). Supramolecular salicylic acid (SSA), a modified SA preparation, is considered as a new effective therapeutic scheme. Objectives To compare the safety and efficacy of 2% supramolecular SA (2% SSA) with 0.01% adapalene plus 5% benzoyl peroxide (5%BPO +0.1%ADA) for treatment of facial acne. Materials and methods This was an open-label, split face, randomized and single-centre clinical trial. Subjects with mild to moderate acne were enrolled. Two percent SSA cream were randomly applied on one side of the face while 5%BPO +0.1%ADA gel was applied on the opposite side for 28 days. The numbers of acne lesions, along with side effects of the targeted area were evaluated by the investigators at day 0, day 14, and day 28. Skin water content, TEWL and skin lightening indexes were measured at the same time. Results A total of 31 of acne patients completed the trial. Dates showed that 2% SSA had similar effects to 5%BPO +0.1%ADA in reducing papules/pustules (47.9% vs. 49.8%), non-inflammatory lesions (43.1% vs. 42.7%) and total lesions (44.1% vs. 45.6%; all p > 0.05) at day 28. The skin barrier (skin hydration value and TEWL value), skin brightness (L* value) and erythema (a* values) indicators showed no statistical differences in the left and right sides of the face (p > 0.05). Conclusion This study demonstrated that 2% SSA has a similar efficacy with 5%BPO +0.1%ADA in mild to moderate acne treatment. This might be a useful pilot study that could be used to support further larger clinical trials.

Codelivery of benzoyl peroxide & adapalene using modified liposomal gel for improved acne therapy.

Current study investigates therapeutic efficacy and tolerability of benzoyl peroxide (BPO)- and adapalene (AD)-loaded modified liposomal gel (BPO-AD-mLipo gel) for improved acne therapy. BPO-AD-mLipo were optimized and loaded in Carbopol gel. Both BPO-AD-mLipo and BPO-AD-mLipo-gel were extensively characterized for different quality attributes. Ex vivo dermal bioavailability, dermal distribution, in vivo anti-acne efficacy and skin irritation studies were performed and compared with marketed formulation (Epiduo®, Galderma Laboratories LP, TX, USA). BPO-AD-mLipo illustrated size 256.4±9.3nm with polydispersity index∼0.2. Significantly enhanced dermal bioavailability (AD-2.1, 5.4; BPO-3.0, 7.83-fold) and reduction in skin irritation and papule density in animal model were observed with BPO-AD-mLipo-gel as compared with free drugs and Epiduo,respectively. BPO-AD-mLipo gel provides effective and safer alternative approach for codelivery of anti-acne drugs.

Adapalene gel 0.1% vs. placebo as prophylaxis for anti-EGFR-induced acne-like rash: A randomized left-right comparative evaluation (APPEARANCE).

10093Background: Anti-EGFR drugs frequently cause acne-like rash. Adapalene (ADP), a topical retinoid used as first-line therapy for acne, is efficacious against acne-like rash induced by anti-EGFR...

Selective delivery of adapalene to the human hair follicle under finite dose conditions using polymeric micelle nanocarriers.

Drug delivery systems that target the pilosebaceous unit (PSU) selectively could improve the clinical management of diseases that originate in the hair follicle. The aims of this study were (i) to prepare polymeric micelles using d-α-tocopheryl polyethylene glycol succinate diblock copolymer that incorporated adapalene (ADA), a retinoid indicated for Acne vulgaris, and (ii) to investigate the feasibility of delivering ADA preferentially to the PSU under finite dose conditions - thereby better approximating actual conditions of use by patients. Incorporation of ADA into spherical micelles (dn <20 nm) increased aqueous solubility by ∼50 000-fold (from <4 ng mL-1 to 0.2 mg mL-1). Optimized micelle solution and gel formulations (0.02% ADA) were stable after storage for 4 weeks at 4 °C. Finite dose experiments using full-thickness porcine and human skin revealed that ADA delivery efficiency from micelle solution and gel formulations was equivalent and was >2- and 10-fold higher than that from Differin® gel and Differin® cream (products containing ADA at 0.1% (w/w)). Follicular delivery studies in human skin, using a punch biopsy technique to extract the intact PSU, demonstrated that the micelle solution and gel formulations did indeed enable preferential delivery of ADA to the PSU (4.5- and 3.3-fold higher, respectively, than that to PSU-free skin biopsies). Confocal laser scanning microscopy provided visual corroboration that ADA was uniformly distributed in the hair follicles. In conclusion, the results confirmed that polymeric micelle nanocarriers enabled selective, targeted drug delivery to the PSU under finite dose conditions and so might improve therapy of follicular diseases and decrease off-site side-effects.

Efficacy and Saftey of Adapalene 0.3%/Benzoyl Peroxide 2.5% Gel Plus Doxycycline in Subjects with Severe Inflammatory Acne (Non-Nodulocystic) that are Candidates for Oral Isotretinoin

Abstract Not Available

Progressive osseous heteroplasia: three case reports

Objective To investigate clinicopathological features, diagnosis and treatment of progressive osseous heteroplasia (POH) . Methods Clinicopathological data were collected from 3 cases of POH, and analyzed retrospectively. Related literature was also reviewed. Results All the 3 patients were female, and developed POH within a few days to months after birth. POH clinically manifested as light pink or skin-colored indurated papules, nodules or plaques scattered over the scalp, trunk and extremities without subjective symptoms. Histopathological examination showed that there were flaky bone or bone-like tissues in the middle and lower dermis. Serum levels of calcium, phosphate and parathyroid hormone were normal in the 3 children. Case 1 was treated with oral sodium bicarbonate tablets and surgical resection of skin lesions on the right lower abdomen. During the follow-up for about 7 months, the skin lesions on the right lower abdomen did not recur, while other skin lesions became more bulging, larger and harder, and new skin lesions occurred. Case 2 was treated with topical adapalene gel, and these skin lesions did not increase in number, but became larger and harder. Case 3 received no treatment, and was lost to follow-up. Conclusion POH clinically manifests as indurated maculopapules and plaques progressively affecting deeper skin tissues, and there are no effective therapies or prevention approaches at present. Key words: Bone diseases, developmental; Skin manifestations; Pathologic processes; Diagnosis; Therapy; Progressive osseous heteroplasia

Mechanistic Analysis of Human Skin Distribution and Follicular Targeting of Adapalene-Loaded Biodegradable Nanospheres With an Insight Into Hydrogel Matrix Influence, In Vitro Skin Irritation, and In Vivo Tolerability

This work aimed at the development of a biocompatible, non-oily nanomedicine for follicular delivery of adapalene (AD) ameliorating its irritation potential for convenient localized topical treatment of acne vulgaris. AD was efficiently incorporated into poly-ε-caprolactone nanospheres (NS) with an encapsulation efficiency of 84.73% ± 1.52%, a particle size of 107.5 ± 8.19 nm, and zeta potential of −13.1 mV demonstrating a sustained-release behavior. The AD-NS were embedded in either hydroxypropyl methylcellulose (HPMC) or hyaluronate (HA) gel. The ex vivo human skin dermatokinetics of AD from each system was studied. The nanoparticles dispersion showed significantly higher AD retention in the epidermis and dermis than AD suspension. NS-HPMC decreased whereas NS-HA increased AD retained in all the skin layers. The fate of the NS and the role of the hydrogel in modulating skin distribution was evaluated by confocal laser scanning microscopy (CLSM) imaging of fluorescently labeled NS. CLSM illustrated follicular localization of the florescent NS. HPMC gel restricted the presence of NS to the stratum corneum and epidermis. HA gel enhanced the penetration of NS to all the skin layers. In vitro skin irritation using human dermal fibroblasts and in vivo animal tolerability studies were performed. Accordingly, HA gel–dispersed AD-NS presented a nonirritant compromised cosmeceutical formulation suitable for oily acneic skin.

Determination of adapalene in gel formulation by conventional and derivative synchronous fluorimetric approaches. Application to stability studies and in vitro diffusion test.

BackgroundAdapalene is a retinoid analogue with actions similar to those of tretinoin. It is used in topical treatment of mild to moderate acne. A survey of the literature reveals that no spectrofluorimetric method has been reported yet for determination of ADP, so it was thought necessary to develop a highly sensitive stability indicating spectrofluorimetric method.ResultsTwo highly sensitive spectrofluorimetric approaches were conducted for the assay of adapalene (ADP) in its gel. In the first approach, ADP exhibits an intense native fluorescence at 389 nm after excitation at 312 nm using borate buffer (pH 7.0)/ethanol system. This approach was successfully applied for routine analysis of ADP in its gel and ideally suited to the in vitro diffusion test. To elucidate the inherent stability of ADP, bulk sample was subjected to different stress conditions as specified by ICH guidelines. The acidic and oxidative degradation products were resolved from the intact drug using second and first derivative synchronous fluorimetry at 346 and 312.45 nm, respectively (the second approach). The synchronous fluorescence was scanned at Δ λ of 80 nm in case of acidic degradation and at Δ λ of 100 nm in case of oxidative degradation. Good linearity was obtained for ADP over the range 2.0–14.0 ng/mL with good correlation coefficient 0.999 in each approach. The approaches were carefully examined in terms of linearity, accuracy and precision. They were suitable for routine quality control laboratory. Moreover, the stability-indicating power of the second approach was ascertained via forced degradation studies.ConclusionsThe proposed approaches were validated and successfully applied for the quantitative assay of a small concentration of ADP in its pharmaceutical gel. The conventional spectrofluorimetry was ideally suited for in vitro diffusion test. Stability studies were also conducted using different forced degradation condition according to ICH recommendation.Graphical abstractSimultaneous determination of ADP and its degradation products.

A synergistic approach of adapalene-loaded nanostructured lipid carriers, and vitamin C co-administration for treating acne

The present study documents the fabrication and characterization of a topically applicable gel loaded with nanostructured lipid carriers (NLCs) of adapalene (ADA) and vitamin C (ascorbyl-6-palmitate [AP]). The NLCs were prepared by high pressure homogenization (HPH) method followed by incorporation into AP loaded gel. The fabricated system was characterized for size, poly dispersity index, entrapment efficiency (EE) and in vitro drug release properties, and was further investigated for skin compliance, skin transport characteristics (skin permeation and bio-distribution), rheological behavior, texture profile analysis and anti-acne therapeutic potential against testosterone-induced acne in male Wistar rats. The NLC-based formulation improved targeting of the skin epidermal layer and reducing systemic penetration. The co-administration of vitamin C led to an adjunct effect in acne therapy in physiological conditions. In brief, the present results suggest the potential of NLCs as a novel carrier for the dermal delivery of ADA and also the synergistic effect of vitamin C in topical therapeutics.

Formulation and evaluation of Adapalene-loaded nanoparticulates for epidermal localization.

Adapalene (ADP), a topically administered antiacne drug, finds limitation due to poor penetration, limited localization, and associated incompatibility of photosensitization and skin irritation. To explicate an innovative and safe method for ADP administration and alleviating the associated limitations, solid lipid nanoparticles (SLN) of ADP have been fabricated and evaluated for efficacy in the present work. The SLN were prepared using pre-emulsion sonication method and incorporated into convenient topical dosage form, hydrogels. In vitro permeation studies of the hydrogels through HCS indicated gel containing ADP-SLN showed 2-fold more accumulation in skin layers as compared to conventional ADP gel. Rheological studies demonstrated ADP-SLN gel to possess pseudoplastic behavior, occlusion and hydration studies revealed permeation effectiveness of ADP-SLN gel over conventional ADP gel while primary skin irritation studies established safety of the ADP-SLN gel upon topical application. Hence, it was concluded that the studied ADP-SLN formulation with skin localizing ability may be a promising carrier for topical delivery of ADP.

Validated Stability-Indicating RP-HPLC Method for the Estimation of Degradation Behaviour of Organic Peroxide and Third-Generation Synthetic Retinoids in Topical Pharmaceutical Dosage Formulation.

The objective of the current study was to establish a validated stability-indicating, high-performance liquid chromatographic method to determine the purity of benzoyl peroxide (BPO) and adapalene (ADP) in the presence of its impurities, forced degradation products, and placebo in pharmaceutical dosage forms. The desired chromatographic separation was achieved on the Kinetex™ C18 (250 × 4.6 mm, 5 µm) column using gradient elution at 272 nm detection wavelength. The optimized mobile phase consisted of solvent A (mixture of 0.1% v/v glacial acetic acid in water and acetonitrile in the ratio of 80:20 v/v, respectively) and solvent B (mixture of acetonitrile: tetrahydrofuran: methanol in the ratio of 50:30:20 v/v/v, respectively). The stability-indicating capability of the developed method was established by analysing forced degradation samples in which the spectral purity of BPO and ADP along with separation of all degradation products from the analyte peaks was achieved. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision, and robustness.

Nodulocystic Acne Regimens

A phase IIIb, multicenter, randomized, investigator-blinded, controlled, parallel group, 20-week noninferiority trial compared two treatments in 217 patients (age, 12–35 years) with severe nodulocystic acne. Eligible patients were randomized to once-daily doses of oral isotretinoin (0.5 mg/kg, escalated to 1 mg/kg after 4 weeks) or oral doxycycline hyclate 200 mg plus topical gel containing both adapalene 0.1% and benzoyl peroxide 2.5% (D+A/BPO). Makers of the A/BPO gel funded the study. At week 2, D+A/BPO …

Adapalene loaded solid lipid nanoparticles gel: An effective approach for acne treatment

Salient features such as controlled release, target ability, potential of penetration, improved physical stability, low cost compared to phospholipids, and ease of scaling-up makes solid lipid nanoparticles (SLNs) a viable alternative to liposomes for effective drug delivery. Adapalene (ADA) is a second generation retinoid effective in treating various dermatologic disorders such as Acne vulgaris with a few noticeable dose-mediated side effects. The present study was aimed at developing and characterizing ADA loaded SLNs for effective topical delivery. The formulated SLN system was characterized for particle size, poly dispersity index, entrapment efficiency and drug release properties. The resultant formulation (ADA loaded SLNs incorporated into carbopol hydrogel) was evaluated for in vitro drug release, skin permeation and bio-distribution, rheological behaviour, and texture profile analysis. The SLNs based ADA gel has shown its potential in targeting skin epidermal layer, and reducing systemic penetration. The developed system can avoid systemic uptake of ADA in skin layers, and can localize drug in skin epidermis as confirmed by rat skin model. Our results advocate potential of SLNs as a novel carrier for topical delivery of ADA in topical therapeutic approaches. This study open new avenues for drug delivery which better meets the need of anti-acne research.

Development and validation of a stability-indicating LC method for the assay of adapalene in bulk drug and pharmaceutical formulations

A simple and sensitive reverse phase HPLC method for the determination of adapalene (ADP) in bulk drug samples and pharmaceutical formulations has been developed and validated. The separation of ADP was achieved on an Inertsil ODS-3V (5 μm, 15 cm ± 4.6 mm i.d.) column using UV detector at 230 nm. The mobile phase consisted of ammonium acetate (25 mM, pH 3.0), methanol and tetrahydrofuran (18: 42: 40 v/v). The linear range of detection was 2–200 μg/mL (R = 0.9991). Intra- and inter-day assay relative standard deviation values were less than 0.5%. The method has been successfully applied to the determination of ADP in pharmaceutical preparations. The excipients commonly present in formulations did not interfere with the assay of ADP. Analytical parameters were calculated and complete statistical evaluation was performed.

Contact dermatitis to the combination gel of adapalene 0.1% and benzoyl peroxide (PBO) 2.5%

ejd.2011.1578 Auteur(s) : Audrey Bulinckx1 audrey.bulinckx@gmail.com, Claire Dachelet1, Alice Leroy1, An Goossens2, Dominique Tennstedt1, Marie Baeck1 1 Department of Dermatology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate, 101200 Brussels, Belgium 2 Department of Dermatology, University Hospital, 3000 Leuven, Belgium A fixed-dose combination gel of adapalene 0.1% and benzoyl peroxide (BPO) 2.5% (Epiduo gel®, Galderma, Bornem, Belgium) is an effective acne vulgaris treatment and offers [...]

Adapalene lotion 0.1% shows comparable tolerability to adapalene cream 0.1% in a split-face comparison

Adapalene lotion 0.1% shows comparable tolerability to adapalene cream 0.1% in a split-face comparison

The Clinic Research of the Combined Adapalene and Acne Pellicles to Treat Women Acne after Puberty

Objective To investigate clinical efficacy and safety of the combined adapalene and acne pellicles to treat women acne after puberty, and find effective treatment. Methods 104 cases of female patients with acne after puberty ,were randomly divided into validation group and control group, the validation group were smeared acne pellicles on acne lesion at noon and 0. 1 % adapalene on night before bed once; while the control group only were smeared adapalene on acne lesion once at night. It was 8 weeks to assess the efficacy and followup observation. Results The validation group cure rate was 36. 5%, the effective rate was 96. 2%, while the control group cure rate was 15.4% and 82. 7% respectively. The cure rate and efficient of two groups were significant differences by chi-square test P ＜ 0. 05. Conclusion The combined adapalene and acne pellicles treatment of female puberty acne had significant effect, mild side effects and meyhod dimple, and easy to accept by the patient. It is worth clinical application. Key words: Acne pellicles; Adapalene; Women acne after puberty