Hugo Almeida

In situ gelling systems: a strategy to improve the bioavailability of ophthalmic pharmaceutical formulations.

The low therapeutic efficacy exhibited by conventional ophthalmic solutions owing to precorneal elimination of the drug, drainage by gravity, nasolacrimal drainage, conjunctival absorption, and the absence of controlled release and of bioadhesive properties, can be overcome by the use of in situ gelling systems. The combination in the same formulation of different in situ gelling polymers with different stimuli-responsiveness mechanisms exploiting the unique physicochemical characteristics of the ocular tissues is one such strategy that has produced improved results compared with conventional systems. As we discuss here, the recent use of biodegradable and biocompatible polymers in colloidal carrier systems has proved to be the most effective strategy, resulting in the exponential increase of the bioavailability of the ophthalmic drugs.

Applications of poloxamers in ophthalmic pharmaceutical formulations: an overview

Introduction: An ideal ophthalmic formulation is one that not only prolongs the contact time of the vehicle on the ocular surface but also slows down the drug elimination. The poor bioavailability and therapeutic response exhibited by the conventional ophthalmic solutions due to pre-corneal elimination of the drug may be overcome by the use of in situ gel forming systems. In situ gelling systems increase the viscosity by changing the pH or temperature in the pre-corneal region and lead to an increase of drug bioavailability by slowing drainage. Poloxamers are polyols with thermal gelling properties which are frequently included in ophthalmic formulations to improve the ocular bioavailability of drugs by increasing vehicle viscosity. Areas covered: An overview on the unique physiological characteristics of ocular globe and the limitations and disadvantages of the conventional ophthalmic pharmaceutical formulations. Readers will appreciate the different strategies to improve the absorption of drugs in the ocular globe, especially the incorporation of poloxamers in ophthalmic formulations, understanding the main advantages of the poloxamers and also learning about the different examples of applications of these polymers in ophthalmic pharmaceutical formulations. Expert opinion: Poloxamers offers a new strategy to improve bioavailability and decrease the side effects induced by the systemic absorption of topically applied ophthalmic drugs.

Applications of polymeric and lipid nanoparticles in ophthalmic pharmaceutical formulations: present and future considerations.

The unique properties and characteristics of ocular tissues and the whole set of defence mechanisms of the ocular globe make the instillation of ocular drugs into a difficult task with a low rate of therapeutic response. One of the challenges for the new generation of ophthalmic pharmaceutical formulations is to increase the bioavailability of drugs administered by the ocular route and, therefore, their therapeutic efficacy. This can be achieved with the use of some strategies that provide an increase in the formulation pre-corneal residence time, mucoadhesion and penetration across the eye tissues. Colloidal carrier systems have been very successfully used for the selective and targeted delivery of drugs for several routes of administration. In this context, nanoparticles prepared with specific polymers or lipids and coated, dispersed or suspended in polymer solutions with mucoadhesion properties or in situ gelling properties will be an excellent strategy that deserves attention and further research. In this review, the characteristics and main properties of polymeric and lipid nanoparticles are discussed and examples and advantages of the application of these colloidal carrier systems for the ophthalmic administration of drugs are presented. The future directions of the research required in this specific field are also presented.

Preparation, characterization and biocompatibility studies of thermoresponsive eyedrops based on the combination of nanostructured lipid carriers (NLC) and the polymer Pluronic F-127 for controlled delivery of ibuprofen

Abstract Context: Nanostructured lipid carrier (NLC) dispersions present low viscosity and poor mucoadhesive properties, which reduce the pre-corneal residence time and consequently, the bioavailability of ocular drugs. Objective: The aim of this study was to prepare thermoresponsive eyedrops based on the combination of lipid nanoparticles and a thermoresponsive polymer with mucomimetic properties (Pluronic® F-127). Materials and methods: NLCi dispersions were prepared based on the melt-emulsification and ultrasonication technique. Physicochemical and morphological characteristics of the colloidal dispersions were evaluated. The formulation was also investigated for potential cytotoxicity in Y-79 human retinoblastoma cells and the in vitro drug release profile of the ibuprofen was determined. Results: NLCi showed a Z-average below 200 nm, a highly positive zeta potential and an efficiency of encapsulation (EE) of ∼90%. The gelification of the NLCi dispersion with 15% (w/w) Pluronic® F-127 did not cause significant changes to the physicochemical properties. The potential NLC-induced cytotoxicity was evaluated by the Alamar Blue reduction assay in Y-79 cells, and no relevant cytotoxicity was observed after exposure to 0–100 µg/mL NLC for up to 72 hours. The optimized formulations showed a sustained release of ibuprofen over several hours. Discussion and conclusion: The strategy proposed in this work can be successfully used to increase the bioavailability and the therapeutic efficacy of conventional eyedrops.

Comparative study of sustained-release lipid microparticles and solid dispersions containing ibuprofen

Ibuprofen is one of the most important non-steroidal anti-inflammatory drugs used in the treatment of inflammatory diseases. In its pure state, ibuprofen presents poor physical and mechanical characteristics and its use in solid dosage forms needs the addition of excipients that improve these properties. The selection of the best excipients and the most suitable pharmaceutical dosage form to carry ibuprofen is very important for the industrial success of this drug. Given these factors, lipid microparticles and solid dispersions of ibuprofen with cetyl alcohol, stearic acid, and hydrogenated castor oil were prepared. These formulations were intended to improve the physical and mechanical characteristics and to sustain the release of this drug. Physical mixtures were also prepared with the same ingredients in similar proportions. The solid dispersions of ibuprofen/stearic acid and ibuprofen/hydrogenated castor oil showed the best flow characteristics compared with pure ibuprofen. Further, gelatin capsules filled with lipid microparticles and solid dispersions were submitted to dissolution tests in order to study the influence of the prepared systems in the release profiles of ibuprofen. Prolonged release of ibuprofen was achieved with the lipid microparticles and solid dispersions prepared with the different types of excipients.

New Thermoresponsive Eyedrop Formulation Containing Ibuprofen Loaded-Nanostructured Lipid Carriers (NLC): Development, Characterization and Biocompatibility Studies

The low bioavailability and consequently the poor therapeutic response of traditional ophthalmic formulations is caused by reduced pre-corneal residence time of the formulation in contact with the ocular surface. The use of colloidal carrier systems, namely lipid nanoparticles in combination with in situ gelling polymers, is an excellent strategy which results in the exponential increase of the bioavailability of ophthalmic drugs. In the present study, we have developed thermoresponsive eyedrops prepared with nanostructured lipid carriers (NLC) dispersions for the controlled delivery of ibuprofen. Lipid solubility studies and DSC measurements have proved that the lipids solubilise ibuprofen and present a good compatibility. NLC were prepared based on the melt-emulsification and ultrasonication technique and lipid nanoparticles with a Z-average of 120-150 nm, polydispersity index below 0.3, highly positive zeta potential and an efficacy of encapsulation of ~87% were obtained. The cytotoxicity of NLC was evaluated by the Alamar Blue reduction assay using the Y-79 human retinoblastoma cell line, and no relevant toxicity was observed after exposure to 0-100 μg/mL NLC for up to 72 hours. The HET-CAM assay was used to assess the product eye compatibility, confirming that the developed product does not exhibit irritant potential. The in vitro release studies showed ibuprofen release over several hours.

Drugs obtained by biotechnology processing

In recent years, the number of drugs of biotechnological origin available for many different diseases has increased exponentially, including different types of cancer, diabetes mellitus, infectious diseases (e.g. AIDS Virus / HIV) as well as cardiovascular, neurological, respiratory, and autoimmune diseases, among others. The pharmaceutical industry has used different technologies to obtain new and promising active ingredients, as exemplified by the fermentation technique, recombinant DNA technique and the hybridoma technique. The expiry of the patents of the first drugs of biotechnological origin and the consequent emergence of biosimilar products, have posed various questions to health authorities worldwide regarding the definition, framework, and requirements for authorization to market such products.

Prolonged-release solid dispersions of ibuprofen

Ibuprofen (IB) is one of the most important non-steroidal anti-inflammatory drugs used in the treatment of inflammatory chronic diseases. This drug presents, in the pure state, poor physical and mechanical characteristics and their use in solid dosage forms needs the addition of excipients which improve these properties. The selection of the best excipients and the suitable pharmaceutical dosage form to carry ibuprofen are very important for the industrial success of this drug. Thus, in this work, solid dispersions of ibuprofen in cethyl alcohol (SD CA), stearic acid (SD SA) and hydrogenated castor oil (SD HCO) were prepared in order to improve physical and mechanical characteristics of this drug. Physical mixtures with the same composition of solid dispersions were also prepared. Solid dispersions of ibuprofen with stearic acid and hydrogenated castor oil showed better flow characteristics than pure ibuprofen and the respective physical mixtures. Gelatin capsules filled with solid dispersions were submitted to dissolution tests in order to study the influence of the prepared systems in the release profiles of ibuprofen. Prolonged-release of ibuprofen was achieved with the solid dispersions prepared with the different types of excipients.

Intranasal Lipid Nanoparticles for the Treatment of Neurodegenerative Diseases

BACKGROUND Current treatments for neurodegenerative diseases are challenging, due to the absence of full effective medicines. One of the major problems associated to these is the occurrence of non-targeting events, which leads to adverse effects and requires frequent dose administration. METHODS Researches have been performed to develop new drug delivery systems administrated by alternative routes. For example, the direct nose-to-brain delivery of drugs by means of lipid nanoparticles, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), have been showing promising results. RESULTS Among the advantages of intranasal administration is the avoidance of passing the blood-brain barrier (BBB) to reach the central nervous system (CNS), allowing the direct delivery of drugs to the brain by a non-invasive way, minimizing systemic exposure and prolonging residence time. This review article discusses the advantages of using SLN and NLC for direct nose-to-brain drug delivery. A brief reference to other lipid-based carriers (liposomes, nanoemulsions and microemulsions) is also provided. CONCLUSION The benefits of using SLN and NLC for improve nasal drug delivery have been demonstrated by in vitro, ex vivo and in vivo experiments. However, more in vivo animal studies are needed for advance to human clinical trials and reach clinics.