A simple drug-delivery microneedling technique modality successfully improves linear atrophic scars.

BACKGROUND: Atrophic scars are white, dermal depressions, caused by the destruction of collagen fibers and decrease in epidermal cells, following inflammation after different types of trauma. They lead to significant physical, aesthetic and psychological barriers and their treatment remain a therapeutic challenge for dermatologists. Microneedling has been shown to improve scars by stimulating angiogenesis and neocolagenesis and the combination of anti-fibrotic drugs could potentialize the results. METHODS: We present 8 cases of patients with linear scars, successfully treated with two sessions of a new Microneedling technique, using a tattoo machine, associated with drug delivery of 5-FU. RESULTS: A marked improvement in scar pigmentation and texture were noted by patients and doctors, 6 months following the sessions of MMP and drug delivery with 5-FU, in different body sites. We also showed that the assessment scores of at least one of the professionals with those of the patient had significant correlations with each other, which shows consistency between the qualitative assessment instruments. We also showed that the cause of the injury can influence joint assessment scores (physicians plus patient) or those exclusive to professionals trained for the assessments, generating evidence that the cause of the injury can influence the treatment outcome itself. CONCLUSIONS: We present an inexpensive and promising approach that can be easily done as an in-office procedure. Larger, multicenter studies are needed to validate this technique among the first line therapies for acne scar treatment.

Preparation of Nanosized Pharmaceutical Formulations by Dual Centrifugation.

Dual centrifugation (DC) is an innovative in-vial homogenization and in-vial nanomilling technique that has been in use for the preparation of liposomes for more than one decade. Since then, DC has continuously been developed for preparing various liposomes and other lipid nanoparticles including emulsions and solid lipid nanoparticles (SLNs) as well as polymersomes and nanocrystals. Improvements in equipment technology have been achieved over the past decade, so that DC is now on its way to becoming the quasi-standard for the simple, fast, and aseptic production of lipid nanoparticles and nanocrystals in small and medium batch sizes, including the possibility of simple and fast formulation screening or bedside preparations of therapeutic nanoparticles. More than 68 publications in which DC was used to produce nanoparticles have appeared since then, justifying an initial review of the use of DC for pharmaceutical nanotechnology.

Processing of Lipid Nanodispersions into Solid Powders by Spray Drying.

Spray drying is a promising technology for drying lipid nanodispersions. These formulations can serve as carrier systems for poorly water-soluble active pharmaceutical ingredients (APIs) that are loaded into the lipid matrix to improve their bioavailability. Once the API-loaded nanocarriers have been further processed into solid dosage forms, they could be administered orally, which is usually preferred by patients. Various solid lipids as well as oils were used in this study to prepare lipid nanodispersions, and it was shown that their nanoparticulate properties could be maintained when lactose in combination with SDS was used as matrix material in the spray-drying process. In addition, for lipid nanoemulsions loaded with fenofibrate, a good redispersibility with particle sizes below 300 nm at a lipid content of 26.8 wt.% in the powders was observed. More detailed investigations on the influence of the drying temperature yielded good results when the inlet temperature of the drying air was set at 110 °C or above, enabling the lactose to form an amorphous matrix around the embedded lipid particles. A tristearin suspension was developed as a probe to measure the temperature exposure of the lipid particles during the drying process. The results with this approach indicate that the actual temperature the particles were exposed to during the drying process could be higher than the outlet temperature.

Embedding of Poorly Water-Soluble Drugs in Orodispersible Films-Comparison of Five Formulation Strategies.

The poor bioavailability of many newly developed active pharmaceutical ingredients (APIs) poses a major challenge in formulation development. To overcome this issue, strategies such as the preparation of amorphous solid dispersions (ASDs), and the application of the APIs in lipid nanocarriers or the wet-milling of the substances into nanoparticles have been introduced. In addition to an efficient formulation strategy, a dosage form that is accepted by all patients is also of great importance. To enable a simple application of the oral dosage form for all patients, orodispersible films (ODFs) are a very promising delivery platform for the APIs because the films directly disintegrate in the mouth. In this study, two poorly water-soluble APIs, fenofibrate and naproxen, were formulated using five different formulation strategies and then embedded in ODFs. It was found that the deliverable amount of API with one ODF highly depends on the formulation strategy as well as the physicochemical properties of the formulated API. The most promising film formulations were ASD-ODFs as well as films with API-loaded lipid nanoemulsions. Both showed a reduction of the dissolution time of the APIs from the ODF compared to an ODF with unformulated API micro particles. In addition, short disintegration times were achieved, although the mechanical film properties were slightly worse compared to the API-free film formulation.

Orodispersible Films: A Delivery Platform for Solid Lipid Nanoparticles?

To overcome the poor bioavailability observed for many newly developed active pharmaceutical ingredients (APIs), an appropriate formulation strategy is necessary. One approach is the formulation of these substances in solid lipid nanoparticles and their further processing into solid dosage forms. A promising and innovative oral delivery platform could be orodispersible films (ODFs). ODFs were already investigated more closely, e.g., for the administration of API nanoparticles, and proved their suitability for this formulation approach. The current study was aimed at investigating if the HPMC (hydroxypropyl methyl cellulose) film matrix is also suitable to serve as an appropriate delivery platform for solid lipid nanoparticles. Dependent on the type of triglyceride nanoparticles embedded in the film matrix and the formulation of the lipid particles, lipid contents of up to 54 wt.% could be realized in the film matrix without the loss of the nanoparticulate state. Good mechanical properties were confirmed for these films by determining the tensile strength as well as the elongation before breakage. Interestingly, processing of a lipid suspension into this solid dosage form led to a significantly reduced transformation of the lipid particles from the metastable α- into the stable ß-polymorph. This could prove very beneficial when the lipid particles are loaded with APIs.

Influence of process and formulation parameters on the preparation of solid lipid nanoparticles by dual centrifugation.

A promising strategy to formulate poorly water-soluble active pharmaceutical ingredients (APIs) is the application of these substances in solid lipid nanoparticles. These drug carrier systems are commonly prepared by high-pressure homogenization above the melting temperature of the utilized lipid. While being very useful for large-scale production this method is quite resource-consuming and does not allow simultaneous processing of multiple samples, e.g. for screening purposes. For this reason, an alternative manufacturing process, dual centrifugation, is introduced to prepare solid lipid nanoparticles. The ingredients of the dispersions were directly weighed into 2 mL vessels at room temperature without the need to prepare a pre-mix emulsion. Due to an additional rotation of the samples in the heated centrifuge as well as the addition of grinding media an intensive stressing of the samples was achieved. The emulsification process was finished within 10 min with sample temperatures of up to 90 °C being obtained. Dependent on the process set-up like grinding media size, filling ratio or process temperature and the composition of the lipid formulation, the achieved particles sizes were below 200 nm and had a narrow, monomodal size distribution.

Treatment of Male-Pattern Alopecia with Platelet-Rich Plasma.

BACKGROUND: Androgenetic alopecia (AGA) affects up to 80% of men and 50% of women throughout their lifetime, causing significant discomfort. Minoxidil, finasteride, and low-level laser light therapy are the only Food and Drug Administration-approved treatments for AGA, and they have shown positive results in randomized controlled trials and meta-analyses. However, their efficacy is limited, and new therapies are needed. Injection of platelet-rich plasma (PRP), a minimally invasive technique, has been described by several authors as a promising treatment for AGA. Although many studies report beneficial effects of PRP on AGA, there is no standardized practice for PRP preparation and administration or a standard method to evaluate results. OBJECTIVE: The aim of this study was to evaluate the efficacy of manually prepared PRP in the treatment of male AGA. MATERIALS AND METHODS: We treated 20 male patients with AGA with 3 monthly injections of PRP and analyzed results by TrichoScan®. RESULTS: In this study, there was no statistically significant improvement in hair count or proportion of anagen hairs. CONCLUSIONS: This lack of response could be related to any of the variables during PRP preparation described above and also to the limited number of patients in the study.

Função da blefaroplastia superior no rejuvenescimento facial / Role of upper blepharoplasty in facial rejuvenation

Notável é a gama de tratamentos faciais, com intuito estético, com os quais podemos preservar o equilíbrio da forma ou a beleza de nossos pacientes. Preenchimentos, toxina botulínica, laser e outras tecnologias são amplamente demonstrados à classe dermatológica. As pálpebras também podem ser tratadas com esses e outros recursos terapêuticos. No entanto, a herniação das bolsas de gordura das pálpebras superiores não tem resultados significativos com esses métodos. O avanço das técnicas conhecidas como minimamente invasivas e das tecnologias não supre a contento o tratamento desta unidade estética facial. Pensando no rejuvenescimento global da face é improvável conseguirmos um resultado de excelência sem atuar nas pálpebras. A blefaroplastia superior segue insubstituível e é o tratamento de escolha para redundância da pele e herniação das bolsas de gordura. Esta cirurgia, com amplo histórico na Dermatologia, tem um papel único e fundamental no rejuvenescimento facial. Procuramos neste estudo demonstrar a técnica cirúrgica de blefaroplastia superior de maneira didática e comprovar sua eficácia e segurança, com bons resultados estéticos e funcionais. Com pleno conhecimento desta região anatômica e dos preceitos técnicos, reconhecemos poder realizá-la com segurança.

It is noteworthy the range of facial treatments, with aesthetic purpose, with which we can preserve the balance of the shape or beauty of our patients. Fillers, botulinum toxin, laser, and other technologies are widely used in dermatology. Eyelids can also be treated with these and other therapeutic resources. However, herniation of the fat pockets of the upper eyelids does not present significant results with these methods. The advancement of techniques known as minimally invasive and other technologies does not satisfy the treatment of this facial aesthetic unit. Thinking about the global rejuvenation of the face, it is unlikely that we will achieve a result of excellence without acting on the eyelids. Upper blepharoplasty remains irreplaceable, and it is the treatment of choice for skin redundancy and herniation of fat pockets. This surgery, with a long history in Dermatology, has a unique and fundamental role in facial rejuvenation. In this study, we tried to demonstrate the surgical technique of superior blepharoplasty educationally and to prove its efficacy and safety, with good aesthetic and functional results. With full knowledge of this anatomical region and technical precepts, we recognize that we can perform it safely.

Estudo comparativo do uso da minociclina sistêmica versus corticoterapia sistêmica no tratamento de vitiligo em atividade / Comparative study on the use of systemic minocycline versus systemic corticosteroid therapy in the treatment of active vitiligo

Introdução: Vitiligo é uma doença cutânea adquirida crônica, que evolui com despigmentação. O controle da atividade da doença é um desafio terapêutico. Os corticosteroides sistêmicos, em uso diário ou sob a forma de pulsos, constituem o tratamento mais utilizado para a doença. Objetivo: Avaliar o efeito da minociclina no controle sobre a atividade do vitiligo em comparação ao corticosteroide. Métodos: Ensaio clínico randomizado com 16 pacientes com vitiligo vulgar em atividade, distribuídos em dois grupos: Grupo MINO - minociclina 100mg/dia, via oral, por três meses; e Grupo CORT - prednisolona 0,3mg/kg/dia, via oral, por dois meses e 0,15mg/ kg/dia no terceiro mês. Os pacientes foram avaliados antes e depois do tratamento por: registros fotográficos e avaliação das pontuações obtidas pelo escore VIDA (escore de atividade da doença vitiligo). Resultados: De acordo com os registros fotográficos, houve controle da atividade do vitiligo em 100% dos pacientes do Grupo MINO em comparação a 60% do Grupo CORT. Na comparação para o escore VIDA, notou-se diferença estatisticamente significante para ambos os grupos; porém, constatou-se que a redução foi maior no Grupo MINO, evidenciando maior efetividade da minociclina no controle da atividade do vitiligo. Conclusões: Este estudo demonstrou a eficácia da minociclina no controle do vitiligo em atividade em comparação a um esquema de corticoterapia sistêmica. Estudos adicionais devem ser realizados para confirmar sua eficácia.

Introduction: Vitiligo is a chronic acquired skin disease, which evolves with depigmentation. The control of disease activity is a therapeutic challenge. Systemic corticosteroids, in daily use or in pulse doses, are the most used treatment for the disease. Objective: To evaluate the effect of minocycline on the control over vitiligo activity compared with the corticosteroid therapy. Methods: Randomized clinical trial with 16 active vitiligo vulgaris patients, divided into two groups: MINO group: minocycline 100mg/day, orally, for three months; and CORT group: prednisolone 0.3mg/kg/day, orally, for two months, and 0.15 mg/kg/day in the third month. The patients were evaluated before and after the treatment by photographic records and evaluation of the scores obtained by the VIDA score (vitiligo disease activity score). Results: According to the photographic records, there was control of vitiligo activity in 100% of patients in the MINO group compared with 60% in the CORT group. In the comparison using the VIDA score, we noticed a statistically significant difference for both groups; however, we found that the reduction was greater in the MINO group, evidencing more effectiveness of minocycline in controlling the vitiligo activity. Conclusion: This study demonstrated the efficacy of minocycline in the control of active vitiligo compared with a systemic corticosteroid regimen. Additional studies should be performed to confirm its efficacy.

SOFTs - Structured orodispersible film templates.

Orodispersible films (ODFs) have a high potential to accelerate the individualized medication. The films can be produced as drug-free templates and subsequently printed with an API (active pharmaceutical ingredient) solution or suspension according to the needs of the patient. While the printing technology already enables a precise dosing of fluids, there is still a high need of suitable, edible templates with elevated loading capacity. The structured orodispersible film templates (SOFTs) developed in this study should overcome this void. The SOFTs are pervaded with pores to realize a high API load into the film structure and possess a closed bottom side to prevent the printed fluids to pass through the film. They consist of a water-soluble cellulose derivative and are produced with the solvent casting method. This study focused on the influence of the formulation of the film casting mass on the film properties, like porosity and disintegration time due to changed pore sizes and numbers. Due to the porous film structure a mass load of up to 6.1 mg cm-2 could be realized already in SOFTs, but, higher loads are feasible. The mechanical film properties could further be improved by additional matrix material in the suspension formulation, also inhibiting particle agglomeration and aggregation during the drying process, and positively influencing the dissolution behavior of the applied nanoparticles. An application of a protection layer on top of the loaded SOFTs improves the handling safety by inhibiting contact to the API and it prevents a removal of the particles from the film surface.

Model-based description of disintegration time and dissolution rate of nanoparticle-loaded orodispersible films.

The embedding of nanoparticles in orodispersible films (ODFs) is an innovative strategy to improve the bioavailability of poorly water-soluble active pharmaceutical ingredients (API). As the films are supposed to disintegrate within seconds when placed in the mouth, the disintegration time of the ODFs as well as the dissolution behavior of the API are of great interest. This study introduces a new possibility for a model-based description of these film properties to enable a prediction for the process layout for the manufacturing of the nanoparticle-loaded ODFs. Furthermore, this fundamental understanding can provide information on process robustness as a tool applied in future Quality by Design (QbD) approaches. The disintegration times of the nanoparticle-containing ODFs were measured with the SFaB method (slide frame and ball) and could be mathematically described considering the impact of the particle load and the dry film thickness on the disintegration behavior. Furthermore, it is considered if the films are disintegrated at the calculated time with a probability of 50% or any other probability. Besides the disintegration time, a clear influence of film parameters like the particle load, size of the embedded particles, film thickness and sample sizes was shown which affect the dissolution rate of the API from the ODF. The second model developed in the study identified a clear correlation between the total surface area of API particles in the film and the dissolution rate of the API, to predict the time period needed to release the API embedded in the ODFs.

Evaluation of oral tranexamic acid in the treatment of melasma.

BACKGROUND: Melasma is an acquired, chronic, recurrent hypermelanosis that occurs exclusively in areas exposed to the sun. Its treatment can be very challenging. Tranexamic acid (TA) is an inhibitor of plasmin, and it is a synthetic derivative of the amino acid lysine that reversibly blocks binding sites on the plasminogen molecule, inhibiting the plasminogen activator from converting plasminogen to plasmin. AIMS: This study evaluated the efficacy of oral TA in the treatment of melasma in patients from a philanthropic dermatological clinic. PATIENTS/METHODS: This was a monocentric, randomized, double-blind, controlled clinical trial. Patients with facial melasma were randomly divided into the following two groups: A (TA 250 mg orally twice daily) or B (oral placebo twice daily). Evaluations were performed before and after 12 weeks of treatment with photographs, colorimetry, MELASQoL, and MASI. All patients were instructed to use tinted sunscreen (SPF 50). RESULTS: Of the 47 patients selected, 37 completed the study, with 20 in group A and 17 in group B; the patients consisted of one male and 36 females, and the mean age was 43.97 years old. Based on the four methods of evaluation, the melasma in 50% of patients in group A improved versus only 5.9% of patients in group B (P < 0.005). There was an improvement according to all evaluation methods in the treatment group. No patient had severe side effects. CONCLUSIONS: We conclude that tranexamic acid was effective in 50% of patients according to four methods of evaluation when compared to the placebo.

Comparative study on disintegration methods for oral film preparations.

Orodispersible films (ODFs) provide high application comfort due to rapid disintegration in the oral cavity. They increasingly found the approval of pharmaceutical research and development and were added to the European Pharmacopeia in 2012. The European Pharmacopeia explicitly demands disintegration testing for ODFs, but does not refer to a suitable method. The aim of this study was to collect and evaluate existing disintegration methods regarding their suitability to investigate different ODF formulations. Therefore, 21 ODF formulations produced at different gap heights and/or different amounts of suspended microcrystalline cellulose (MCC) particles were manufactured by solvent casting technique, using hypromellose (HPMC) as film-forming polymer. Four disintegration methods described in literature were applied to characterize the disintegration behavior of these formulations. They were the petri dish, the slide frame, slide frame and ball (SFaB) method as well as the PharmaTest® disintegration tester equipped with a film sample holder. All methods show similar tendencies, at which the disintegration time proportionally increases with increasing dry film thicknesses. Reduced disintegration times were observed for ODFs containing insoluble MCC particles compared to their corresponding particle-free formulations. However, the suitability to investigate varying types of ODFs applying the four different test methods highly depends on the intended purpose. Therefore, the slide frame and SFaB method seems to be particularly applicable for research and development purposes, whereas the PharmaTest® disintegration tester and the SFaB method fulfil the demands required for testing methods within the quality control.

Quality of life before and after cosmetic procedures on the face: A cross-sectional study in a public service.

BACKGROUND: Quality of life can be impaired by health conditions that modify body appearance. AIMS: The objective of this cross-sectional study was to evaluate the quality of life of patients before and after free-of-charge esthetic dermatological treatments offered in a philanthropic Dermatological Clinic for nonpathological conditions, such as anti-aging procedures. METHODS: All consecutive patients admitted between March and November 2016 were recruited. All esthetic treatments in this study were simple procedures applied in one session only, on the face, neck, arms, and upper chest, with a consult visit scheduled four weeks later for clinical evaluation. The WHOQOL-BREF instrument was used before and one month after the procedure. RESULTS: WHOQOL-BREF scores increased significantly after treatment (P < 0.001) in all the domains. CONCLUSION: Patients undergoing simple dermatological treatments applied by specialists report overall and specific domain improvements in quality of life, according to the World Health Organization instrument, regardless of the type of procedure.

Apresentação exuberante de caso de esclerose sistêmica / Exuberant presentation in a case of systemic sclerosis

A esclerose sistêmica (ES) é doença autoimune do tecido conjuntivo de etiologia desconhecida, caracterizada pela esclerose (fibrose), que afeta a pele, vasos sanguíneos e órgãos internos. O diagnóstico é firmado pelo quadro clínico compatível, pesquisa de autoanticorpos e capilaroscopia do leito ungueal. Destaca-se neste relato a importância do médico dermatologista frente ao diagnóstico de doenças sistêmicas. Na observação da pele, visível e palpável em todas as suas dimensões e na interpretação de todos os seus sinais, conclui-se que é possível revelar precocemente problemas internos que poderiam evoluir de forma oculta.

Systemic sclerosis (SE) is an autoimmune disease of the connective tissue. Of unknown etiology, it is characterized by sclerosis (fibrosis), which affects the skin, blood vessels and internal organs. The diagnosis is confirmed by a compatible clinical picture, autoantibody research and capillaroscopy of the nail bed. The present report highlights the importance of the dermatologist physician in the diagnosis of systemic diseases. Based on the observation of the skin ­ which is visible and palpable in all of its dimensions ­ and in the interpretation of all its signs, it is possible to conclude that it can reveal early internal disorders that could develop unnoticeably.

Tratamento de psoríase vulgar pela microinfusão de medicamentos na pele (MMP®) usando ciclosporina e metotrexato / Treatment of psoriasis vulgaris with cyclosporine and methotrexate injections using the MMP® technique

Medicações sistêmicas orais como ciclosporina (CYA) ou metotrexato (MTX) para tratamento de psoríase tem biodisponibilidade limitada devido à absorção incompleta gastrointestinal e metabolização de primeira passagem hepática. Além disso, estão associados a efeitos adversos. A aplicação de CYA ou MTX através da Microinfusão de Medicamentos pela pele (MMP®) para tratamento de psoríase vulgar mostrou resposta terapêutica com redução significativa de lesões, sem indução de efeitos colaterais. Neste relato, descrevemos 4 casos de psoríase vulgar tratados com MMP® com CYA ou MTX.

Systemic oral medications ­ such as cyclosporine (CYA) or methotrexate (MTX) ­ for the treatment of psoriasis have limited bioavailability due to incomplete gastrointestinal absorption and first-pass hepatic metabolism. Moreover, they are associated with adverse effects. The application of CYA or MTX using the microinfusion of drugs into the skin method (MMP®) for the treatment of psoriasis vulgaris yielded a therapeutic response with significant reduction of lesions, and absence of side effects. In the present report, the authors describe 4 cases of psoriasis vulgaris treated using the MMP® method, with the application of CYA or MTX.

Novel strategies for the formulation and processing of poorly water-soluble drugs.

Low aqueous solubility of active pharmaceutical ingredients presents a serious challenge in the development process of new drug products. This article provides an overview on some of the current approaches for the formulation of poorly water-soluble drugs with a special focus on strategies pursued at the Center of Pharmaceutical Engineering of the TU Braunschweig. These comprise formulation in lipid-based colloidal drug delivery systems and experimental as well as computational approaches towards the efficient identification of the most suitable carrier systems. For less lipophilic substances the preparation of drug nanoparticles by milling and precipitation is investigated for instance by means of microsystem-based manufacturing techniques and with special regard to the preparation of individualized dosage forms. Another option to overcome issues with poor drug solubility is the incorporation into nanospun fibers.