Development and Characterization of New Miconazole-Based Microemulsions for Buccal Delivery by Implementing a Full Factorial Design Modeling.

This research aimed to develop miconazole-based microemulsions using oleic acid as a natural lipophilic phase and a stabilizer mixture comprising Tween 20 and PEG 400 to solubilize miconazole as an antifungal agent known for its activity in oral candidiasis and to improve its bioavailability. The formulation and preparation process was combined with a mathematical approach using a 23-full factorial plan. Fluid and gel-like microemulsions were obtained and analyzed considering pH, conductivity, and refractive index, followed by extensive analyses focused on droplet size, zeta potential, rheological behavior, and goniometry. In vitro release tests were performed to assess their biopharmaceutical characteristics. Independent variables coded X1-Oleic acid (%, w/w), X2-Tween 20 (%, w/w), and X3-PEG 400 (%, w/w) were analyzed in relationship with three main outputs like mean droplet size, work of adhesion, and diffusion coefficient by combining statistical tools with response surface methodology. The microemulsion containing miconazole base-2%, oleic acid-5%, Tween 20-40%, PEG 400-20%, and water-33% exhibited a mean droplet size of 119.6 nm, a work of adhesion of 71.98 mN/m, a diffusion coefficient of 2.11·10-5 cm2/s, and together with remarked attributes of two gel-like systems formulated with higher oil concentrations, modeled the final optimization step of microemulsions as potential systems for buccal delivery.

Electrospun PCL Wires Loaded with Vancomycin on Zirconium Substrate.

The current study presents research about electrodeposition in relation to electrospinning PCL wires on a Zr substrate and loading the coating with vancomycin. The structural composition of the coatings was investigated via FT-IR analysis. The morphology evaluated using scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy, for the composition (SEM-EDS), evidenced the presence of the polymer wires, with and without drug vancomycin loading. The wettability of the coatings was evaluated from the hydrophobic-hydrophilic point of view, and the characterization was completed with mechanical and electrochemical tests. All the electrochemical tests performed in simulated body fluid highlighted that PCL represents a barrier against corrosion processes. The quantitative method to evaluate the loading efficiency shows that almost 80% of the total loaded vancomycin is released within 144 h; after the initial burst at 24 h, a steady release of vancomycin is observed over 7 days. A kinetic model of the drug release was also constructed.

The Influence of the Polymer Type on the Quality of Newly Developed Oral Immediate-Release Tablets Containing Amiodarone Solid Dispersions Obtained by Hot-Melt Extrusion.

The present study aims to demonstrate the influence of the polymer-carrier type and proportion on the quality performance of newly developed oral immediate-release tablets containing amiodarone solid dispersions obtained by hot-melt extrusion. Twelve solid dispersions including amiodarone and different polymers (PEG 1500, PEG 4000; PEG 8000, Soluplus®, and Kolliphor® 188) were developed and prepared by hot-melt extrusion using a horizontal extruder realized by the authors in their own laboratory. Only eleven of the dispersions presented suitable physical characteristics and they were used as active ingredients in eleven tablet formulations that contain the same amounts of the same excipients, varying only in solid dispersion type. The solid dispersions' properties were established by optical microscopy with reflected light, volumetric controls and particle size evaluation. In order to prove that the complex powders have appropriate physical characteristics for the direct compression process, they were subjected to different analyses regarding their flowability and compressibility behavior. Additionally, the Fourier transform infrared spectroscopy and X-ray diffraction analysis were performed on the obtained solid dispersions. After confirming the proper physical attributes for all blends, they were processed into the form of tablets by direct compression technology. The manufactured tablets were evaluated for pharmacotechnical (dimensions-diameter and thickness, mass uniformity, hardness and friability) and in vitro biopharmaceutical (disintegration time and drug release) performances. Furthermore, the influence of the polymer matrix on their quality was determined. The high differences in flow and compression performances of the solid dispersions prove the relevant influence of the polymer type and their concentration-dependent plasticizing properties. The increase in flowability and compressibility characteristics of the solid dispersions could be noticed after combining them with direct compression excipients owning superior mechanical qualities. The influence of the polymer type is best detected in the disintegration test, where the obtained values are quite different between the studied formulations. The use of PEG 1500 alone or combined in various proportions with Soluplus® leads to rapid disintegration. In contrast, the mixture of PEG 4000 and Poloxamer 188 in equal proportions determined the increase in disintegration time to 120 s. The use of Poloxamer 188 alone and a 3:1 combination of PEG 4000 and Soluplus® also generates a prolonged disintegration time for the tablets.

Formation and Physico-Chemical Evaluation of Nifedipine-hydroxypropyl-ß-cyclodextrin and Nifedipine-methyl-ß-cyclodextrin: The Development of Orodispersible Tablets.

The novelty in this study is the development of new orodispersible tablets containing nifedipine (NIF) as the active ingredient. Initially, the formation of inclusion complexes between nifedipine and two derivatives of beta-cyclodextrin, namely, hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and methyl-ß-cyclodextrin (Me-ß-CD), was established. Inclusion complexes of nifedipine were prepared by different procedures: kneading, coprecipitation and lyophilization methods, using a 1:1 molar ratio among the drug and cyclodextrin compounds. A physical mixture was also developed for comparison, with the same molar ratio. The physicochemical and structural properties of these obtained complexes were subsequently analysed using Fourier-transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry and X-ray diffraction techniques. The lyophilization method of preparation leads to obtaining the complete inclusion of nifedipine in the used cyclodextrin cavity, for both the derivative cyclodextrins. After that, preformulation studies and manufacturing of orodispersible tablets containing NIF-HP-ß-CD and NIF-Me-ß-CD, respectively, inclusion complexes were advanced. The obtained findings show that only F3 (which contains NIF-HP-ß-CD) and F6 (which contains NIF-Me-ß-CD) have a suitable flowability for the direct compression materials.

Square root law model for the delivery and intestinal absorption of drugs: a case of hydrophilic captopril.

The in vivo release and absorption of drugs are dependent on the interplay between many factors related to compound, formulation, and physiological properties. The mathematical models of oral drug absorption attempt to strike a balance between a complete description that takes into consideration as many independent factors as possible, and simple models that operate with fewer parameters, based mainly on critical factors. The latter models are by far more robust and easier to apply to predict the extent and sometimes even the rate of absorption. The present paper attempted to develop a simple model to describe the time course of absorption of the hydrophilic drug captopril (CPT) at the early phases of absorption, with implications mainly in the induction and early stages of achieving its therapeutic effect. As a phenomenological model, the instantaneous release of CPT was considered in the gastrointestinal fluid, leading to a constant drug concentration for a prolonged time, followed by a 'long path diffusion' inside the intestinal wall and a very low concentration at the interface intestinal wall-blood. These conditions regarding CPT concentration were translated into initial and boundary mathematical conditions for the diffusion equation in the intestinal wall. The solution of the diffusion equation led in the end to a square root law describing the dependence between the fraction of the drug absorbed and time. The model was successfully applied to data obtained in five bioequivalence studies: three comparing plasma levels achieved after the administration of a single dose of CPT 50 mg, one evaluating CPT pharmacokinetics after a 100 mg dose, and a fifth comparing CPT pharmacokinetics of two fixed-dose combinations of CPT 50 mg and hydrochlorothiazide 25 mg.

Formulation of Chewable Tablets Containing Carbamazepine-ß-cyclodextrin Inclusion Complex and F-Melt Disintegration Excipient. The Mathematical Modeling of the Release Kinetics of Carbamazepine.

Due to its low solubility, carbamazepine (CBZ) exhibits slow and incomplete release in the gastrointestinal tract and, hence, variable pharmacokinetics and pharmacodynamic effect. Lots of methods have been devised to improve its solubility, the large number of proposed solutions being a sign that the problem is not yet satisfactorily solved. The persistent problem is that predictable release kinetics, an increased rate but within defined limits, are required to avoid high absorption variability. This paper presents a synthesis of a carbamazepine-ß-cyclodextrin inclusion complex (CBZ-ß-CD), the characterization of the physical mixture, CBZ, ß-CD and the CBZ-ß-CD inclusion complex using Fourier transform infrared spectroscopy, scanning electron microscopy, simultaneous thermal analysis and X-ray diffraction, formulation of chewable tablets, determination of the dissolution of carbamazepine in medium containing 1% sodium lauryl sulfate (LSS), and in simulated saliva (SS), mathematical modeling of release kinetics. The kinetics of total CBZ release from tablets containing CBZ-ß-CD and super-disintegrant F-Melt in both SS and LSS followed two steps: a burst release in the first minutes and a slower release in intervals up to 60 min. The release in the second phase has been well described by the Higuchi and Peppas models, which advocate a controlled release by combined diffusion and with some phenomena of swelling and relaxation of the matrix generated by the crospovidone component of the F-Melt excipient.

Foray into Concepts of Design and Evaluation of Microemulsions as a Modern Approach for Topical Applications in Acne Pathology.

With a fascinating complexity, governed by multiple physiological processes, the skin is considered a mantle with protective functions which during lifetime are frequently impaired, triggering dermatologic disorders. As one of the most prevalent dermatologic conditions worldwide, characterized by a complex pathogenesis and a high recurrence, acne can affect the patient's quality of life. Smart topical vehicles represent a good option in the treatment of a versatile skin condition. By surpassing the stratum corneum known for diffusional resistance, a superior topical bioavailability can be obtained at the affected place. In this direction, the literature study presents microemulsions as a part of a condensed group of modern formulations. Microemulsions are appreciated for their superior profile in matters of drug delivery, especially for challenging substances with hydrophilic or lipophilic structures. Formulated as transparent and thermodynamically stable systems, using simplified methods of preparation, microemulsions have a simple and clear appearance. Their unique structures can be explained as a function of the formulation parameters which were found to be the mainstay of a targeted therapy.

Sources of outlier data in the bioanalytical and clinical part of a piroxicam bioequivalence study.

OBJECTIVE: This paper analyzes the potential outliers in the bioanalytical and clinical part of a bioequivalence study, the effect on bioequivalence decisions whether or not it is appropriate to eliminate them from the statistical evaluation of bioequivalence. MATERIALS AND METHODS: The clinical part was a cross-over, two periods, two sequences bioequivalence study concerning two piroxicam formulations, on healthy subjects. A simulation study evaluated the influence of 10% errors on the percent bias of calculated concentrations from nominal ones. RESULTS: In bioequivalence studies, it is not possible to distinguish between relevant types of outliers based only on statistical criteria. The "problem" is particularly acute when the omission of outliers leads to a bias in the decision concerning bioequivalence from rejection to acceptance. In such cases, there is the suspicion of subjective analysis and torture of data. The effect of analytical errors at high plasma levels was criticized for the calculated concentrations in the neighborhood of lower limit of quantification. Errors at low concentrations have a less significant effect. In the pharmacokinetic analysis, several types of outliers were shown: single points, curves, pairs of curves corresponding to the same subject, intrasubject ratios of areas under curves and maximum concentrations. These pharmacokinetic outliers could have had, at the same time, bioanalytical, physiological and physicochemical causes. CONCLUSION: Considering the results, it was proposed the following algorithm in the analysis of outlier data and outlier subjects in bioequivalence studies: evaluation of the implications of the decision concerning elimination of outliers on the decision concerning bioequivalence; application of the statistic tests for detection of outliers data; evaluations from the point of view of physiological pharmacokinetics, final decision concerning elimination of outliers.

Development and Characterization of Orally Disintegrating Tablets Containing a Captopril-Cyclodextrin Complex.

Captopril is the first angiotensin I-converting enzyme inhibitor widely used for the treatment of hypertension. Based on the well-known benefits of cyclodextrin inclusion complexes, the present study investigated the ability of ß-cyclodextrin to include captopril. Solid inclusion complexes of captopril with ß-cyclodextrin in a 1:2 molar ratio were prepared by using the paste method of complexation. For comparison purposes, a simple physical mixture with the same molar ratio was also prepared. Fourier-transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and simultaneous thermal analysis were used to characterize the raw materials, physical mixture and solid inclusion complex. In order to provide the drug in a more accessible and patient-compliant form following masking its bitter taste, as well as ensuring the appropriate release kinetics, the investigated complex was formulated as orally disintegrating tablets. The study of captopril dissolution in both compendial and simulated saliva media suggested the Noyes Whitney model as the best mathematical model to describe the release phenomena. A clinical study on healthy volunteers also highlighted the taste improvement of the new formulation as compared to conventional tablets.

Estimation of the In Vivo Release of Amiodarone From the Pharmacokinetics of Its Active Metabolite and Correlation With Its In Vitro Release.

Due to its very low water solubility and complex pharmacokinetics, a reliable point-to-point correlation of its in vitro release with its pharmacokinetics has not been achieved so far with amiodarone. The correlation of the in vitro dissolution of a drug with the pharmacokinetics of one of its metabolites was recently proposed by the authors of the article as an additional or alternative analysis to the usual in vitro correlations in vivo, mainly in the case of fast-absorbing drugs that have metabolites with a significant therapeutic effect. The model proposed by the authors considers that amiodarone has a slow dissolution, rapid absorption, and rapid metabolism, and before returning to the blood from other compartments, its pharmacokinetics is determined mainly by the kinetics of release in the intestine from the pharmaceutical formulation. Under these conditions, the rate of apparition of desethylamiodarone in the blood is a metric of the release of amiodarone in the intestinal fluid. Furthermore, it has been shown that such an estimated in vivo dissolution is similar, after time scaling, to the dissolution measured experimentally in vitro. Dissolution data of amiodarone and the pharmacokinetic data of its active metabolite desethylamiodarone were obtained in a bioequivalence study of 24 healthy volunteers. The elimination constant of the metabolite from plasma was estimated as the slope of the linear regression of logarithmically transformed data on the tail of plasma levels. Because the elimination of desethylamiodarone was shown to follow a monoexponential model, a Nelson-Wagner-type mass equilibrium model could be applied to calculate the time course of the "plasma metabolite fraction." After Levi-type time scaling for imposing the in vitro-in vivo correlation, the problem became that of the correlation between in vitro dissolution time and in vivo dissolution time, which was proven to follow a square root model. To validate the model, evaluations were performed for the reference drug and test drug separately. In both cases, the scaled time for in vivo dissolution, t*, depended approximately linearly on the square root of the in vitro dissolution time t, with the two regression lines being practically parallel.

Pharmacokinetics of B-Ring Unsubstituted Flavones.

B-ring unsubstituted flavones (of which the most widely known are chrysin, baicalein, wogonin, and oroxylin A) are 2-phenylchromen-4-one molecules of which the B-ring is devoid of any hydroxy, methoxy, or other substituent. They may be found naturally in a number of herbal products used for therapeutic purposes, and several have been designed by researchers and obtained in the laboratory. They have generated interest in the scientific community for their potential use in a variety of pathologies, and understanding their pharmacokinetics is important for a grasp of their optimal use. Based on a comprehensive survey of the relevant literature, this paper examines their absorption (with deglycosylation as a preliminary step) and their fate in the body, from metabolism to excretion. Differences among species (inter-individual) and within the same species (intra-individual) variability have been examined based on the available data, and finally, knowledge gaps and directions of future research are discussed.

Effect of a New Synergistic Combination of Low Doses of Acetylsalicylic Acid, Caffeine, Acetaminophen, and Chlorpheniramine in Acute Low Back Pain.

The present paper continues a more complex research related to the increased synergism in terms of both anti-inflammatory and analgesic effect obtained by the addition of chlorpheniramine (CLF) to the common acetylsalicylic acid (ASA), acetaminophen (PAR), and caffeine (CAF) combination. This synergistic effect was previously highlighted both in vitro in rat models and in vivo in the treatment of migraine. The aim of the research was to further evaluate the analgesic effect of a synergistic low-dose ASA-PAR-CAF-CLF combination in the treatment of low back pain, in a parallel, multiple-dose, double-blind, active controlled clinical trial. A number of 89 patients with low back pain of at least moderate intensity were randomly assigned to receive Algopirin® (ALG), a combinational product containing 125 mg ASA, 75 mg PAR, 15 mg CAF, and 2 mg CLF, or PAR 500 mg, a drug recognized by American Pain Society as "safe and effective" in the treatment of low back pain. One tablet of the assigned product was administered three times a day for seven consecutive days. The patients evaluated their pain level using a Visual Analog Scale prior to administration, and at 1, 2, 4, and 6 h after the morning dose. Time course of effect was similar in structure and size for both treatments. Pain relief appeared rapidly and steadily increased over 4 h after drug administration. Differential pain curves of ALG and PAR were very similar and comparable with the previously determined ALG analgesia pattern in migraine. Differences between the daily mean pain scores were not statistically significant for the two treatments. Similar results were obtained for the Sum of Pain Intensity Differences (SPID) for 0-4 h and 0-6 h intervals as well as for the time course of the proportion of patients with at least 30% and at least 50% pain relief. In conclusion, in spite of very small doses of active components, ALG proved equally effective to the standard low back pain treatment and therefore a viable therapeutic alternative, mainly for patients with gastrointestinal and hepatic sensitivity. Trial Registration: www.ClinicalTrials.gov, identifier EudraCT No.: 2015-002314-74.

In Vitro-In Vivo Correlations Based on In Vitro Dissolution of Parent Drug Diltiazem and Pharmacokinetics of its Metabolite.

In this study a novel type of in vitro-in vivo correlation (IVIVC) is proposed: The correlation of the in vitro parent drug dissolution data with the in vivo pharmacokinetic data of drug's metabolite after the oral administration of the parent drug. The pharmacokinetic data for the parent drug diltiazem (DTZ) and its desacetyl diltiazem metabolite (DTZM) were obtained from an in vivo study performed in 19 healthy volunteers. The pharmacokinetics of the parent drug and its metabolite followed a pseudomono-compartmental model and deconvolution of the DTZ or DTZM plasma concentration profiles was performed with a Wagner-Nelson-type equation. The calculated in vivo absorption fractions were correlated with the in vitro DTZ dissolution data obtained with USP 2 apparatus. A linear IVIVC was obtained for both DTZ and DTZM, with a better correlation observed for the case of the metabolite. This type of correlation of the in vitro data of the parent compound with the in vivo data of the metabolite could be useful for the development of drugs with active metabolites and prodrugs.

Predictive power of the Triticum root elongation test for the assessment of novel anti­proliferative therapies.

The use of alternative techniques to reduce the number of animals used in anticancer research is an issue of current interest. The aim of this study was to validate the use of a simple and efficient alternative tool for the assessment of the potential of novel anti­proliferative agents. A set of 20 compounds with various mechanisms were tested in the Triticum aestivum root elongation assay, using aminophylline as negative control. Hierarchical cluster analyses were performed using the furthest neighbor method based on Euclidean distance measure, and the compounds were statistically analyzed in reference to their anti­proliferative pattern registered in the NCI60 human tumor cell line anticancer drug screen. A correlation between the Triticum test results and the NCI60 anti­proliferative profile was made for a number of human cells that we defined as the Triticum cell panel. Linear equations were computed that can be used to transform the inhibitory effect measured in any future Triticum assay in order to predict the effect on particular human cells. Of the tested anti­proliferative agents, methotrexate, colchicine, cantharidin, cisplatin and verapamil produced a growth inhibition over 50%. On the whole, the findings of this study suggest that the Triticum test can be used to detect several types of anti­proliferative mechanisms, particularly those targeting tubulin, rendering it a useful tool with which to identify novel mitotic spindle inhibitors.

Leonurus cardiaca L. as a Source of Bioactive Compounds: An Update of the European Medicines Agency Assessment Report (2010).

Leonurus cardiaca L. (motherwort) is a perennial herb, native to Asia and southeastern Europe, with widespread global occurrence in present days. The plant was historically used as cardiotonic and for treating gynaecological afflictions (such as amenorrhea, dysmenorrhea, menopausal anxiety, or postpartum depression). Although its use in oriental and occidental medicine is relatively well documented, the recent progress registered raises the need for an update of the Medicines Agency assessment report on Leonurus cardiaca L., herba (2010). The current study presents the progress made within the 2010-2018 timeframe regarding the potential applications and scientific evidences supporting the traditional use of motherwort, in the same time suggesting future research opportunities.

Mathematical Modeling of Release Kinetics from Supramolecular Drug Delivery Systems.

Embedding of active substances in supramolecular systems has as the main goal to ensure the controlled release of the active ingredients. Whatever the final architecture or entrapment mechanism, modeling of release is challenging due to the moving boundary conditions and complex initial conditions. Despite huge diversity of formulations, diffusion phenomena are involved in practically all release processes. The approach in this paper starts, therefore, from mathematical methods for solving the diffusion equation in initial and boundary conditions, which are further connected with phenomenological conditions, simplified and idealized in order to lead to problems which can be analytically solved. Consequently, the release models are classified starting from the geometry of diffusion domain, initial conditions, and conditions on frontiers. Taking into account that practically all solutions of the models use the separation of variables method and integral transformation method, two specific applications of these methods are included. This paper suggests that "good modeling practice" of release kinetics consists essentially of identifying the most appropriate mathematical conditions corresponding to implied physicochemical phenomena. However, in most of the cases, models can be written but analytical solutions for these models cannot be obtained. Consequently, empiric models remain the first choice, and they receive an important place in the review.

Phytochemical Profile and Biological Activities of Satureja hortensis L.: A Review of the Last Decade.

Satureja hortensis L. (summer savory) is an annual herbaceous crop, native to Europe and in our days spread and used all over the world. Although its use as spice and medicinal plant is known since ancient times, peer-reviewed studies presenting the scientific data are scarce. The natural products obtained from summer savory (extracts and essential oil) are dominated by polyphenols and flavonoids, responsible for their antioxidant, antimicrobial, antiparasitic, pesticidal, anti-inflammatory, analgesic, hepatoprotective and anticancer properties, among others. The current study presents the progress made in the last decade regarding the potential applications of summer savory, being the first review study focused on S. hortensis, in the same time suggesting future research opportunities, as they appear from the properties of other Satureja species. The available data presenting the properties of summer savory represents a scientific support for application in industry, for developing "clean label" food products.

Genoprotective, antioxidant, antifungal and anti-inflammatory evaluation of hydroalcoholic extract of wild-growing Juniperus communis L. (Cupressaceae) native to Romanian southern sub-Carpathian hills.

BACKGROUND: Juniperus communis L. represents a multi-purpose crop used in the pharmaceutical, food, and cosmetic industry. Several studies present the possible medicinal properties of different Juniperus taxa native to specific geographical area. The present study aims to evaluate the genoprotective, antioxidant, antifungal and anti-inflammatory potential of hydroalcoholic extract of wild-growing Juniperus communis L. (Cupressaceae) native to Romanian southern sub-Carpathian hills. METHODS: The prepared hydroethanolic extract of Juniperus communis L. was characterized by GC-MS, HPLC, UV-Vis spectrometry and phytochemical assays. The antioxidant potential was evaluated using the DPPH assay, the antifungal effect was studied on Aspergillus niger ATCC 15475 and Penicillium hirsutum ATCC 52323, while the genoprotective effect was evaluated using the Allium cepa assay. The anti-inflammatory effect was evaluated in two inflammation experimental models (dextran and kaolin) by plethysmometry. Male Wistar rats were treated by gavage with distilled water (negative control), the microemulsion (positive control), diclofenac sodium aqueous solution (reference) and microemulsions containing juniper extract (experimental group). The initial paw volume and the paw volumes at 1, 2, 3, 4, 5 and 24 h were measured. RESULTS: Total terpenoids, phenolics and flavonoids were estimated to be 13.44 ± 0.14 mg linalool equivalent, 19.23 ± 1.32 mg gallic acid equivalent, and 5109.6 ± 21.47 mg rutin equivalent per 100 g of extract, respectively. GC-MS characterization of the juniper extract identified 57 volatile compounds in the sample, while the HPLC analysis revealed the presence of the selected compounds (α-pinene, chlorogenic acid, rutin, apigenin, quercitin). The antioxidant potential of the crude extract was found to be 81.63 ± 0.38% (measured by the DPPH method). The results of the antifungal activity assay (for Aspergillus niger and Penicillium hirsutum) were 21.6 mm, respectively 17.2 mm as inhibition zone. Test results demonstrated the genoprotective potential of J. communis undiluted extract, inhibiting the mitodepressive effect of ethanol. The anti-inflammatory action of the juniper extract, administered as microemulsion in acute-dextran model was increased when compared to kaolin subacute inflammation induced model. CONCLUSION: The hydroalcoholic extract obtained from wild-growing Juniperus communis native to Romanian southern sub-Carpathian hills has genoprotective, antioxidant, antifungal and anti-inflammatory properties.

Strategies for Improving Ocular Drug Bioavailability and Corneal Wound Healing with Chitosan-Based Delivery Systems.

The main inconvenience of conventional eye drops is the rapid washout of the drugs due to nasolacrimal drainage or ophthalmic barriers. The ocular drug bioavailability can be improved by either prolonging retention time in the cul-de-sac or by increasing the ocular permeability. The focus of this review is to highlight some chitosan-based drug delivery approaches that proved to have good clinical efficacy and high potential for use in ophthalmology. They are exemplified by recent studies exploring in-depth the techniques and mechanisms in order to improve ocular bioavailability of the active substances. Used alone or in combination with other compounds with synergistic action, chitosan enables ocular retention time and corneal permeability. Associated with other stimuli-responsive polymers, it enhances the mechanical strength of the gels. Chitosan and its derivatives increase drug permeability through the cornea by temporarily opening tight junctions between epithelial cells. Different types of chitosan-based colloidal systems have the potential to overcome the ocular barriers without disturbing the vision process. Chitosan also plays a key role in improving corneal wound healing by stimulating the migration of keratinocytes when it is used alone or in combination with other compounds with synergistic action.