Daniela Dal Molim Ghisleni

Nanoemulsion: process selection and application in cosmetics--a review.

In recent decades, considerable and continuous growth in consumer demand in the cosmetics field has spurred the development of sophisticated formulations, aiming at high performance, attractive appearance, sensorial benefit and safety. Yet despite increasing demand from consumers, the formulator faces certain restrictions regarding the optimum equilibrium between the active compound concentration and the formulation base taking into account the nature of the skin structure, mainly concerning to the ideal penetration of the active compound, due to the natural skin barrier. Emulsion is a mixture of two immiscible phases, and the interest in nanoscale emulsion has been growing considerably in recent decades due to its specific attributes such as high stability, attractive appearance and drug delivery properties; therefore, performance is expected to improve using a lipid‐based nanocarrier. Nanoemulsions are generated by different approaches: the so‐called high‐energy and low‐energy methods. The global overview of these mechanisms and different alternatives for each method are presented in this paper, along with their benefits and drawbacks. As a cosmetics formulation is reflected in product delivery to consumers, nanoemulsion development with prospects for large‐scale production is one of the key attributes in the method selection process. Thus, the aim of this review was to highlight the main high‐ and low‐energy methods applicable in cosmetics and dermatological product development, their specificities, recent research on these methods in the cosmetics and consideration for the process selection optimization. The specific process with regard to inorganic nanoparticles, polymer nanoparticles and nanocapsule formulation is not considered in this paper.

The Microbial Quality Aspects and Decontamination Approaches for the Herbal Medicinal Plants and Products: An in-Depth Review.

BACKGROUND The present review article provides an overview of the published literature concerning microbial quality of medicinal plants and products and their decontamination methods. It is important to analyze different aspects regarding the cultivation, growing, harvesting, storage, manufacturing, and decontamination of medicinal plant products. Herbal medicinal plants bear a massive microbial load leading to contamination and mycotoxin, which needs to be considered, and properly controlled using suitable sterilization and decontamination methods. METHODS The main focus of this review is on the definition, advantages, disadvantages and applications of decontamination methods, particularly to show that one must consider the characteristics of the initial sample to be decontaminated. RESULTS The effects of various methods (ozone, plasma, irradiation) on medicinal herbs and products treated for microbiological decontamination are dependent on factors related to microbial load (i.e., nature and amount of initial contamination), herb/product matrix (i.e., complexity of chemical composition, physical state - solid or liquid) and treatment conditions (i.e., time, irradiation dose, absence or presence of oxygen). In addition, it is important to accept some loss of the chemical compounds, while decreasing microbial load to acceptable limits according to official herbal pharmacopoeias and literature, thus ensuring a final product with quality, safety and therapeutic efficacy. CONCLUSION The conclusion, which comes from this contribution, is that herbal medicine has more contaminants than a chemically welldefined drug, thus, good manufacturing practices should be followed.

Sterilization of silicone-based hydrogels for biomedical application using ozone gas: Comparison with conventional techniques

Sterilization of hydrogels is challenging due to their often reported sensitivity to conventional methods involving heat or radiation. Although aseptic manufacturing is a possibility, terminal sterilization is safer in biological terms, leading to a higher overall efficiency, and thus should be used whenever it is possible. The main goal of this work was to study the applicability of an innovative ozone gas terminal sterilization method for silicone-based hydrogels and compare its efficacy and effects with those of traditional sterilization methods: steam heat and gamma irradiation. Ozone gas sterilization is a method with potential interest since it is reported as a low cost green method, does not leave toxic residues and can be applied to thermosensitive materials. A hydrogel intended for ophthalmological applications, based on tris(trimethylsiloxy)silyl] propyl methacrylate, was prepared and extensively characterized before and after the sterilization procedures. Alterations regarding transparency, swelling, wettability, ionic permeability, friction coefficient, mechanical properties, topography and morphology and chemical composition were monitored. Efficacy of the ozonation was accessed by performing controlled contaminations and sterility tests. In vitro cytotoxicity testes were also performed. The results show that ozonation may be applied to sterilize the studied material. A treatment with 8 pulses allowed sterilizing the material with bioburdens≤103CFU/mL, preserving all the studied properties within the required known values for contact lenses materials. However, a higher exposure (10 pulses) led to some degradation of the material and induced mild cytotoxicity. Steam heat sterilization led to an increase of swelling capacity and a decrease of the water contact angle. Regarding gamma irradiation, the increase of irradiation dose led to an increase of the friction coefficient. The higher dose (25kGy) originated surface degradation and affected the mechanical properties of the hydrogel by inducing a significant increase of the Youngs modulus. Overall, the results show that ozonation may be considered as a valid and promising alternative for the sterilization of silicon-based hydrogels for biomedical applications.

Hydrogel based Drug Delivery Systems: A Review with Special Emphasis on Challenges Associated with Decontamination of Hydrogels and Biomaterials

BACKGROUND Many researches involving the development of new techniques and biomaterials to formulate a suitable drug delivery system and tissue engineering have been conducted. The majority of published literature from these researches emphasizes the production and materials characterization. The safety aspect of hydrogels and biomaterials is a major constraint in their biological applications. OBJECTIVE The present review article aimed to summarize various literatures that encompass the difficulties encountered with decontamination and sterilization methods in the preparations of biomaterials and especially hydrogels for biological applications. METHOD We searched for original and review articles from various indexed journals reporting applications of hydrogels and biomaterials in drug delivery systems and the importance of decontamination process for hydrogel containing preparations based on various patents evidences. RESULTS Despite the vast literature available, limited information regarding the decontamination and sterilization processes related to hydrogels and biomaterials is reported. Sterilization processes to hydrogels are not yet fully explored. Researchers working on hydrogel based systems can consider decontamination of such biomaterial as an important tool to allow for commercialization within the chemical, herbal or pharmaceutical industries. CONCLUSION Unfortunately, till date, limited papers are available which reported the challenges associated with decontamination methods to prepare hydrogels and biomaterials for biological applications. In conclusion, each case of biomaterial requires individual consideration to decontamination and/or sterilization. This must be submitted to a specific method, but more than one technique can be involved. Physicochemical and biological alterations must be avoided and evaluated by the appropriate assays method. Furthermore, it is also important to consider that each method must be validated depending upon the process variables.

Dual crosslinked pectin–alginate network as sustained release hydrophilic matrix for repaglinide

Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1h. Developing a controlled and prolonged release delivery system is required to maintain its therapeutic plasma concentration and to eliminate its adverse effects particularly hypoglycemia. The present study aimed to develop controlled release repaglinide loaded beads using sodium alginate and pectin with dual cross-linking for effective control of drug release. The prepared beads were characterized for size, percentage drug entrapment efficiency, in vitro drug release and the morphological examination using scanning electron microscope. For the comparative study, the release profile of a marketed conventional tablet of repaglinide (Prandin® tablets 2mg, Novo Nordisk) was determined by the same procedure as followed for beads. The particle size of beads was in the range of 698±2.34-769±1.43μm. The drug entrapment efficiency varied between 55.24±4.61 to 82.29±3.42%. The FTIR results suggest that there was no interaction between repaglinide and excipients. The XRD and DSC results suggest partial molecular dispersion and amorphization of the drug throughout the system. These results suggest that repaglinide did not dissolve completely in the polymer composition and seems not to be involved in the cross-linking reaction. The percent drug release was decreased with higher polymer concentrations. In conclusion, the developed beads could enhance drug entrapment efficiency, prolong the drug release and enhance bioavailability for better control of diabetes.

Performance Survey and Comparison Between Rapid Sterility Testing Method and Pharmacopoeia Sterility Test

The sterility test described in pharmacopoeial compendia requires a 14-day incubation period to obtain a valid analytical result. Therefore, the use of alternative methods to evaluate the sterility of pharmaceuticals, such as the BacT/Alert® 3D system, is particularly interesting, because it allows a reduced incubation period and lower associated costs. Considering that the BacT/Alert® 3D system offers several culture media formulations developed for this microbial detection system, the present study was aimed to evaluate and compare the performance of BacT/Alert® 3D with the pharmacopoeial sterility test. There was no significant difference between the ability of the culture media to allow detection of microbial contamination. However, the rapid sterility testing method allowed a more rapid detection of the challenge microorganisms, which indicates that the system is a viable alternative for assessing the sterility of injectable products.

Comparison of dissolution profile of extended-release oral dosage forms - two one-sided equivalence test

O objetivo deste trabalho e apresentar o teste uni-caudal duplo (TOST) como uma abordagem alternativa na comparacao do perfil de dissolucao de formas farmaceuticas de liberacao prolongada. Os perfis de dissolucao de comprimidos de liberacao prolongada de oxicodona contendo 10 mg, 20 mg e 40 mg (generico e referencia) foram avaliados de acordo com os requisitos descritos na Farmacopeia Americana. Estes perfis de dissolucao foram comparados empregando-se o fator de semelhanca convencional (f2) e o metodo TOST como teste de equivalencia. TOST e uma abordagem simples e alternativa para a comparacao de perfis de dissolucao de formas farmaceuticas de liberacao prolongada. Este permite identificar o ponto (ou pontos) que nao apresentou semelhanca. Considerando-se D = 10, concluimos que o teste uni-caudal duplo num nivel de significância de 5% apresenta resultados comparaveis aqueles obtidos com o fator de semelhanca convencional (f2).

Drug-eluting silicone hydrogel for therapeutic contact lenses: Impact of sterilization methods on the system performance

Although contact lenses are promising platforms for ocular drug delivery and have been extensively studied for that purpose, the influence of sterilization methods on these systems remains barely investigated. In this work, a silicone-based hydrogel was produced and loaded with different ophthalmic drugs: levofloxacin, chlorhexidine, diclofenac and timolol. The drug release profiles, along with several material properties, were evaluated before and after sterilization by three different methods steam heat, γ-irradiation and ozone gas. Independently of the sterilization method used, the results of the swelling and mechanical properties tests strongly indicate the occurrence of specific drug-polymer interactions promoted by the sterilization. In general, these interactions led to a decrease on the amount of drug released. It is shown that γ-irradiation and ozone led to significant degradation of all of the drugs used in this study. Thus, it was concluded that steam heat is the sterilization method with less impact on the devices. More importantly, the present work shows that the development of efficient and functional drug delivery devices for ophthalmic purposes cannot be done independently of a careful analysis of the influence of the sterilization procedures and methods on the degradation of these polymeric systems as a whole.

Evaluation of an Amplified ATP Bioluminescence Method for Rapid Sterility Testing of Large Volume Parenteral

The sterility test described in pharmacopeial compendia requires a 14-day incubation period to obtain a valid analytical result. Therefore, the use of alternative methods to evaluate the sterility of pharmaceuticals, such as the Celsis AKuScreen™ Advance™ system, is particularly interesting because it allows a reduced incubation period and higher efficiency. The present study was aimed to evaluate and compare the performance of Celsis AKuScreen™ Advance™ system with the pharmacopeial sterility test. There was no significant difference between the ability of detection of microbial contamination observed within pharmacopeial method and test method. The Celsis AKuScreen™ Advance™ system allowed a faster detection of the challenge microorganisms, which indicates that the system is a viable alternative for assessing the sterility of injectable products.