In vitro dissolution/release methods for mucosal delivery systems

In vitro dissolution/release tests are an indispensable tool in the drug product development, its quality control and the regulatory approval process. Mucosal drug delivery systems are designed to provide both local and systemic drug action following ocular, nasal, oromucosal, vaginal or rectal administration. They exhibit significant differences in formulation design, physicochemical characteristics and drug release properties. Therefore it is not possible to devise a single method which would be suitable for release testing of such versatile and complex dosage forms. Different apparatuses and techniques for in vitro release testing for mucosal delivery systems considering the specific conditions at the administration site are described. In general, compendial apparatuses and methods should be used as a first approach in method development when applicable. However, to assure adequate simulation of conditions in vivo, novel biorelevant in vitro dissolution/release methods should be developed. Equipment set up, the selection of dissolution media and volume, membrane type, agitation speed, temperature, and assay analysis technique need to be carefully defined based on mucosal drug delivery system characteristics. All those parameters depend on the delivery system and physiological conditions at the site of application and may vary in a wide range, which will be discussed in details

In vitro dissolution/release methods for mucosal delivery systems

In vitro dissolution/release tests are an indispensable tool in the drug product development, its quality control and the regulatory approval process. Mucosal drug delivery systems are designed to provide both local and systemic drug action following ocular, nasal, oromucosal, vaginal or rectal administration. They exhibit significant differences in formulation design, physicochemical characteristics and drug release properties. Therefore it is not possible to devise a single method which would be suitable for release testing of such versatile and complex dosage forms. Different apparatuses and techniques for in vitro release testing for mucosal delivery systems considering the specific conditions at the administration site are described. In general, compendial apparatuses and methods should be used as a first approach in method development when applicable. However, to assure adequate simulation of conditions in vivo, novel biorelevant in vitro dissolution/release methods should be developed. Equipment set up, the selection of dissolution media and volume, membrane type, agitation speed, temperature, and assay analysis technique need to be carefully defined based on mucosal drug delivery system characteristics. All those parameters depend on the delivery system and physiological conditions at the site of application and may vary in a wide range, which will be discussed in details

Terapijski sustavi za vaginalnu primjenu

The vaginal route of drug administration offers certain unique features that can be exploited in order to achieve desirable therapeutic effects. Considerable progress has been made in this research area over the past few years and, at present, the anatomy and physiology, microflora and secretions of the vagina are well understood. By contrast, the scientific knowledge regarding the possibilities of drug delivery via the vagina is limited. To date, there are only a limited number of vaginal dosage forms available, although various possibilities are explored. Pharmaceutical dosage forms far vagina! delivery are usually applied far the local treatment of specific gynaecological diseases, such as candidiasis, vaginosis and sexually transmitted diseases. The currently available vaginal delivery systems have some limitations, such as leakage, messiness and low residence time, which contribute to poor subject or patient compliance. Therefore, attempts are being made to develop novel vagina! drug delivery systems (e.g. bioadhesive systems, liposomes) that can meet the clinical and user's requirements. This review is focused on the various aspects, scope and potential of vaginal drug delivery

Liposomi kao nosači lijekova: strukturna svojstva i klasifikacija

Liposomes are colloidal particles in which a phosholipid bilayer membrane, composed from self-assembled amphiphlic molecules encapsulates pare of the aqueous phase in which they are dispersed. Since their discovery in the mid-1960s, they were first used to study biological membranes. Due to their biodegradability and biocompatibility, today, liposomes are useful system for the delivery or targeting of drugs to specific sites in the body. Liposomes are characterized by their phospholipid composition, particle size, number of lamellae, and inner/outer aqueous phases, all of which dictate their stability and inceraction characteristics. They are able to incorporate almost any drug regardless of solubility, or to carry on their surface cell-specific ligands. Therefore, liposomes have the potential to be tailored in a variety of ways to ensure the production of formulations that are optimal far clinical use. Morphologically, we distinguish between small, medium-sized, large and giant unilamellar, oligoor multi-lamellar, as well as multivesicular liposomes. With respect to inceraction properties there are several types of liposomes: conventional liposomes which are characterized by a nonspecific reactivity of the milieu, sterically stabilized liposomes that are relatively inert and therefore nonreactive to the environment, immunoliposomes and polymorphic liposomes which are very reactive towards specific agents

Liposomi kao nosači lijekova: metode priprave

The key point to grasp in considering the manufacture of liposomes is that phospholipid membranes form spontaneously as a result of unfavourable interactions between phospholipids and water. Thus the emphasis in making liposomes is not towards assembling the membranes (which happens on its own accord), but towards getting the membranes to form vesicles of the right size and structure, and to entrap drugs with high efficiency and in such a way chat they do not leak out of the liposome once formed. All methods of making liposomes involve three or four basic stages: drying down of lipids from organic solvents, dispersion of the lipids in aqueous media, purification of the resultant liposomes and analysis of the final product. The main difference between the various methods of manufacture is in the way in which the membrane components are dispersed in aqueous media, before being allowed to coalesce in the form of bilayer sheets. The methods are classified according to three basic modes of dispersion: physical dispersion, two-phase dispersion and detergent solubilization

Current Trends in Development of Liposomes for Targeting Bacterial Biofilms

Biofilm targeting represents a great challenge for effective antimicrobial therapy. Increased biofilm resistance, even with the elevated concentrations of very potent antimicrobial agents, often leads to failed therapeutic outcome. Application of biocompatible nanomicrobials, particularly liposomally-associated nanomicrobials, presents a promising approach for improved drug delivery to bacterial cells and biofilms. Versatile manipulations of liposomal physicochemical properties, such as the bilayer composition, membrane fluidity, size, surface charge and coating, enable development of liposomes with desired pharmacokinetic and pharmacodynamic profiles. This review attempts to provide an unbiased overview of investigations of liposomes destined to treat bacterial biofilms. Different strategies including the recent advancements in liposomal design aiming at eradication of existing biofilms and prevention of biofilm formation, as well as respective limitations, are discussed in more details

(Phospho)lipid-based nanosystems for skin administration

Nanotechnology and nanomedicine provide a platform for advanced therapeutic strategies for dermal and transdermal drug delivery. The focus of this review is on the current state-of-art in lipid-based nanotechnology and nanomedicine for (trans)dermal drug therapy. Drug delivery nanosystems based on the (phospho)lipid constituents are characterized and compared, with the emphasis on their ability to assure the controlled drug release to the skin and skin appendages, drug targeting and safety. Different types of liposomes, biphasic vesicles, particulate lipid-based nanosystems and micro- and nano-emulsions are discussed in more details. Extensive research in preclinical studies has shown that numerous parameters including the composition, size, surface properties and their combinations affect the deposition and/or penetration of carrier-associated drug into/through the skin, and consequently determine the therapeutic effect. The superiority of the most promising nanopharmaceuticals has been confirmed in clinical studies. We have selected several common skin disorders and provided overview over promises of nanodermatology in antimicrobial skin therapy, anti-acne treatment, skin oncology, gene delivery and vaccines. We addressed the potential toxicity and irritation issues and provided an overview of registered lipid-based product

Hidrogelovi za vaginalnu primjenu lijekova

The vaginal route of drug administration has been used for achieving local and systemic drug effects. The rate and extent of drug absorption after intravaginal application may be altered by vaginal physiology, age, stage in the menstrual cycle, pathological condition and formulation factors. Among a variety of vaginal dosage forms available, hydrogels offer several advantages such as hydrophilicity, biocompatibility, good distribution and retention, appropriate drug release and acceptability by patients. They have been mostly used for the treatment of vaginal dryness and local delivery of antimicrobial drugs, microbicides, contraceptives and labor inducers. However, hydrogels have also potential for systemic delivery of hormones, vaccines, proteins and peptides. This paper summarizes potentials, current use and research on hydrogels as vaginal drug delivery systems

Liposomi s kalceinom: odabir optimalne metode priprave

The aim of our study was to develop a liposomal drug carrier system able to provide appropriate trapping efficiency of hydrophilic substance. Since majority of hydrophilic drugs are of low molecular weight, calcein was chosen as a model compound. To optimize the preparation of liposomes with regard to size and entrapment efficiency, liposomes containing calcein were prepared by different methods: conventional and modified film methods as well as proliposome method. Additionally, a dehydration-rehydration procedure was applied on the liposomes prepared by the both film methods. Ali preparations were extruded through polycarbonate membrane filters to achieve liposomes with homogenous size distribution. Regardless of the preparation method, all extruded liposomes were of mean diameter between 240 and 280 nm. However, encapsulation of calcein into liposomes differed far various preparation methods. Liposomes prepared by the modified film method could entrap more of the hydrophilic marker than those prepared by the conventional hydration method. Although the dehydration- rehydration procedure could slightly enhance the trapping of calcein into liposomes prepared by conventional film method, the extremely high encapsulation of calcein was achieved into proliposomes (> 40 %). Therefore, the proliposome method would be the right choice of preparation procedure far entrapment of hydrophilic substances

Lipidne vezikule za (trans)dermalnu primjenu lijekova

Since liposomes were first shown to be of potential value for topical therapy by Mezei and Gulasekharam in 1980, studies continued towards further investigation and development of lipid vesicles as carriers for skin delivery of drugs. Despite this long history of intensive research, lipid vesicles are stil considered as a controversial class of dermal and transdermal carriers. Accordingly, this article provides an overview of the development of lipid vesicles for skin delivery of drugs with special emphasis on recent advances in this field, including development of deformable liposomes and ethosomes