Ocular Inserts Research Articles

MeltSerts technology (brinzolamide ocular inserts via hot-melt extrusion): QbD-steered development, molecular dynamics, in vitro, ex vivo and in vivo studies

The research work aimed to develop a robust sustained release biocompatible brinzolamide (BRZ)-loaded ocular inserts (MeltSerts) using hot-melt extrusion technology with enhanced solubility for glaucoma management. A 32 rotatable central composite design was employed for the optimization of the MeltSerts to achieve sustained release. The effect of two independent factors was examined: Metolose® SR 90SH-100000SR (HPMC, hydroxypropyl methyl cellulose) and Kolliphor® P 407 (Poloxamer 407, P407). The drug release (DR) of BRZ at 0.5 h and 8 h were adopted as dependent responses. The factorial analysis resulted in an optimum composition of 50.00 % w/w of HPMC and 15.00 % w/w of P407 which gave % DR of 9.11 at 0.5 h and 69.10 at 8 h. Furthermore, molecular dynamic simulations were performed to elucidate various interactions between BRZ, and other formulation components and it was observed that BRZ showed maximum interactions with HPC and HPMC with an occupancy of 92.82 and 52.87 %, respectively. Additionally, molecular docking studies were performed to understand the interactions between BRZ and mucoadhesive polymers with ocular mucin (MUC-1). The results indicated a docking score of only −5.368 for BRZ alone, whereas a significantly higher docking score was observed for the optimized Meltserts −6.977, suggesting enhanced retention time of the optimized MeltSerts. SEM images displayed irregular surfaces, while EDS analysis validated uniform BRZ distribution in the optimized formulation. The results of the ocular irritancy studies both ex vivo and in vivo demonstrated that MeltSerts are safe for ocular use. The results indicate that the developed MeltSerts Technology has the potential to manufacture ocular inserts with cost-effectiveness, one-step processability, and enhanced product quality. Nonetheless, it also offers a once-daily regimen, consequently decreasing the dosing frequency, preservative exposure, and ultimately better glaucoma management.

SELECTION AND JUSTIFICATION OF DRYING IN OCULAR INSERT DEVELOPMENT

Relevance. This study describes aspects of drying in the development of ocular inserts, parameters affecting the kinetics of moisture loss by film-forming polymers of various nature, as well as features of the equipment used in the technological process. Objective. The aim of the study is to develop methods for drying the basis of an innovative ocular medicinal insert intended for the treatment of bac-terial infections. Materials and methods. A film-forming agent of natural origin - hydroxyethylcellulose (Natrosol™ HHX 250, Ashland, USA) was used to prepare the polymer base. Glycerin (Tula Pharmaceutical Factory LLC, Russia) was added as a substance that gives the insert elasticity and plasticity, as well as an excipient that increases bioadhesion, poloxamer (Kolliphor® P 188, BASF, Germany). Purified water was used to dissolve the substances. Placebo inserts were dried outdoors, in a dehydrator (Kitfort KT-1908, China), a thermostat (BINDER BD 56 Avantgarde.Line, Germany), freeze dryer (Harvest right, USA) and vacuum dryer (HETO CT/DW 60 E, Jouan, Gydevang, Denmark). The finished polymer base was evaluated according to the pa-rameters humidity (gravimetric), bioadhesion (separation force), biodegradation time, thickness (micrometer) and elasticity. Results and discussion. Drying of the bases turned out to be less prolonged in a dehydrator, in contrast to the technology carried out in a thermo-stat, freeze dryer and in an open space. Despite the increased drying time in a freeze dryer with a single mode, the parameters of the polymer base did not have significant differences, while ensuring the sterility of the process and the possibility of using an active pharmaceutical ingredient of differ-ent nature. Conclusion. The selection of equipment for drying technology is carried out in accordance with the main parameters - ventilation, temperature con-stancy, humidity, vacuum, the possibility of carrying out the process in sterile conditions, and also the physico-thermal features of reducing the mois-ture of the dosage form are taken into account. The optimal ratio of drying parameters provides a polymer base at the output, which has certain phys-ical properties that characterize the quality indicators of the future drug in the form of an ocular insert. Keywords:

Formulation And Evaluation of Controlled Release Bromfenac Sodium Ocular Insert

According to the World Health Organization, cataract operations are performed on one million people per year [1]. After cataract surgery, however, most patients still experience physiologically severe postoperative ocular inflammation. Uncontrolled intraocular inflammation causes discomfort, delayed recovery, poor visual results, and even more severe problems such as cystoid macular oedema and synechiae due to inflammatory cells and cytokines entering the aqueous humour. Topical non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat non-infectious ocular inflammation after ophthalmic surgery. As a result, NSAIDs appear to be potentially useful drugs for cataract surgery. [2] The U.S Food and Drug Administration has approved four ophthalmic NSAIDs to treat postoperative ocular inflammation followed by cataract surgery: bromfenac sodium, diclofenac sodium, Ketorolac tromethamine, and nepafenac.[3] The first approved NSAID for treating anterior chamber inflammation during cataract surgical treatment is bromfenac ophthalmic solution. Bromfenac is a more potent drug than other drugs for treating ocular inflammation. [4] The drug-loaded eye drop is easy to use. However, it has the inherent disadvantage that most medication is almost immediately diluted away in the tear film when the eye drops are introduced into the cul-de-sac and quickly exhausted from the precorneal cavity's constant tear flow. This process occurs more intensively in swollen eyes than in normal eyes and lachrymal-nasal drainage. [5,6] To avoid the previously stated side effects and increase the drug's effectiveness, a novel approach of an ocular insert that increases the drug's contact time in the eye should be chosen, thus improving patient compliance by increasing bioavailability and reducing frequent administration. [7] Ophthalmic inserts are skinny discs of polymeric substances that fit into the upper or lower conjunctiva sac. They have compensations over the conventional dosage forms and possess amplified ocular residence, discharge the drugs at a slow and consistent momentum, are capable of delivering precise dosing, lack preservatives, have augmented shelf life, and reduced systemic incorporation. [8] Our research intended to fabricate bromfenac sodium ocular inserts to amplify the contact time and offer a controlled release model that could advance patient compliance, cut dosing frequency, and attain superior curative usefulness.

Preparation and In-vitro Evaluation of Timolol Maleate Loaded Ocular inserts by using various polymers

The anatomy physiology and biochemistry of the eye render this organ impervious to foreign substances. Ocusert system was firstly developed in 1975 in the USA. It is a flat, flexible, solid and semisolid device which consists of drug reservoir by using various polymers. In the present study Timolol maleate loaded ocular inserts were prepared using different polymers (Methylcellulose, Hydroxypropyl methylcellulose, Eudragit, Ethyl cellulose, Polyvinyl pyrrolidone) by solvent casting method for the treatment of glaucoma. Glycerin, Polyethylene glycol and Dibutyl phthalate were used as plasticizers in different ratios. The prime objective of ocuserts formulating is to enhance therapeutic effect through continuous controlled delivery of ophthalmically active drug to the eye. The physiochemical parameters like thickness, weight, surface pH, folding endurance, % moisture absorption, % moisture loss and drug content were evaluated. In-vitro drug release studies were carried out using a Franz diffusion cell like model. Drug-polymer interactions were investigated by Fourier transform infrared (FTIR) spectroscopy. It was found that the higher the polymer percentage in the formula, the greater the weight and thickness of the film. The mechanical properties of the films reveal that the formulations (F2, F3, F4, F5, F6, F7 and F8) were strong, elastic with smooth surface and appropriate weight for ocular use. In addition to having surface pH that matches the requirements of the ocular dosage forms. It has also been shown that the formulas with hydrophobic polymers have low ability to absorb moisture as well as low moisture content. F4 (Eudragit RL 100 10%) gave sustained drug release with most of the drug being released after 8 hours (95.331%). The release profile of F4 followed the Korsmeyer-Peppas model and correlation coefficient (R2 = 0.992). FTIR studies did not show any evidence of interaction between the drug and the polymers.

Preparation and Evaluation of Nanofibrous and Film-Structured Ciprofloxacin Hydrochloride Inserts for Sustained Ocular Delivery: Pharmacokinetic Study in Rabbit's Eye.

Conventional anti-infective eye drops are the most common forms of drugs prescribed for the management of topical ocular infections. Despite their convenience, topical eye drops face multiple challenges, including limited bioavailability and repetitive administration. The present study aimed to prepare, evaluate, and compare film-structured and nanofibrous ocular inserts using biocompatible polymers of polyvinyl alcohol (PVA) and polycaprolactone (PCL) to achieve sustained ciprofloxacin Hydrochloride (CIP) delivery. The nanofibrous formulations were prepared by electrospinning and glutaraldehyde crosslinking while the film formulation was prepared by solvent casting. Nanofibrous inserts had mean diameters in the range 330-450 nm. Both film and nanofibrous inserts were strong, although the nanofibers had higher flexibility. In vitro antibacterial efficacy against Staphylococcus aureus and Escherichia coli was observed for all formulations and cell viability of more than 70% confirmed their non-toxicity. In vitro release studies showed prolonged release of 2 days for the film and 5 days for the nanofibers compared with a 10-h release of CIP from the eye drop. Pharmacokinetic studies of rabbits' eyes showed 4.5-5-folds higher AUC for the nanofiber formulations compared with the eye drop. Thus, prolonged-release film-structured and nanofibrous inserts are suitable carriers for ocular delivery of CIP.

Innovation in the Development of Synthetic and Natural Ocular Drug Delivery Systems for Eye Diseases Treatment: Focusing on Drug-Loaded Ocular Inserts, Contacts, and Intraocular Lenses

Nowadays, ocular drug delivery still remains a challenge, since the conventional dosage forms used for anterior and posterior ocular disease treatments, such as topical, systemic, and intraocular administration methods, present important limitations mainly related to the anatomical complexity of the eye. In particular, the blood-ocular barrier along with the corneal barrier, ocular surface, and lacrimal fluid secretion reduce the availability of the administered active compounds and their efficacy. These limitations have increased the need to develop safe and effective ocular delivery systems able to sustain the drug release in the interested ocular segment over time. In the last few years, thanks to the innovations in the materials and technologies employed, different ocular drug delivery systems have been developed. Therefore, this review aims to summarize the synthetic and natural drug-loaded ocular inserts, contacts, and intraocular lenses that have been recently developed, emphasizing the characteristics that make them promising for future ocular clinical applications.

The role of Eudragit® as a component of hydrogel formulations for medical devices.

Over the last decade, significant progress has been made in developing hydrogels as medical devices. By physically cross-linking pharmaceutically approved polymers into three-dimensional matrices, we can ensure their biocompatibility and facilitate their seamless transition from the laboratory to clinical applications. Moreover, the reversible nature of their physical cross-links allows hydrogels to dissolve in the presence of external stimuli. Particularly, their high degree of hydration, high molecular weight, and superior flexibility of the polymer chains facilitate their interaction with complex biological barriers (e.g., mucus layer), making them ideal candidates for mucosal drug delivery. However, fine-tuning the composition of the hydrogel formulations is of great importance to optimize the performance of the medical device and its therapeutic cargo. Herein, we investigated the influence of different Eudragits® on the properties of hydrogels based on polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and polyethylene glycol (PEG), which were originally proposed as ocular inserts in previous reports. Our research aims to determine the effects that including different Eudragits® have on the structure and protein ocular delivery ability of various hydrogel formulations. Properties such as matrix stability, protein encapsulation, release kinetics, mucoadhesion, and biocompatibility have been analyzed in detail. Our study represents a guideline of the features that Eudragits® have to exhibit to endow hydrogels with good adhesion to the eye's conjunctiva, biocompatibility, and structural strength to cope with the ocular biointerface and allow sustained protein release. This work has important implications for the design of new hydrogel materials containing Eudragits® in their composition, particularly in mucosal drug delivery.

Formulation and In-Vitro Evaluation of Sustained Release Pilocarpine Ocuserts Using Modified Karaya Gum Extracted from Sterculia urens

Ocular inserts of Pilocarpine nitrate (PN) were prepared using modified karaya gum (MKG) alone as release retarding polymer and in combination with the copolymer sodium alginate. Modification of the karaya gum was done by treating it with the trisodium trimetaphosphate (STMP) by cross linking method and evaluated for its physicochemical properties. Films of the MKG were prepared by employing solvent casting method using varying concentrations (600mg, 500mg and 400mg) of MKG and the sandwiching technique was used for the loading of drug. Sodium alginate (SA) and PN blend were prepared by triturating their appropriate amounts. Six ocusert formulations (F1-F6) were prepared with different concentrations of the polymer i.e MKG and SA while the amount of PN was kept constant in formulations. Formulations F1-F3 contained the MKG alone in varying concentrations (600mg, 500mg and 400mg) and F4-F6 contained SA (0.5 mg) in addition to MKG. The surface pH of prepared ocuserts from the formulations (F1-F6) was in the range of 6.63 to 6.8. Thickness range of the ocuserts was from 0.21 to 0.32 mm. Dissolution profiles of prepared ocuserts were studied and drug release was found within the range of 69.2± 1.36 % (F4, minimum) to 90.5± 3.21% (F3, maximum). Overall results of the study concluded that ocuserts fabricated with MKG and SA at optimized concentrations have the potential to sustain the release of PN and therefore reducing dosing frequency and adverse effects.

Design and optimization of ciprofloxacin hydrochloride biodegradable 3D printed ocular inserts: Full factorial design and in-vitro and ex-vivo evaluations: Part II

Coupling hot-melt extrusion (HME) with fused deposition modeling three-dimensional printing (FDM-3DP) can facilitate the fabrication of tailored, patient-centered, and complex-shaped ocular dosage forms. We fabricated ciprofloxacin HCl ocular inserts by coupling high-throughput, solvent-free, and continuous HME with FDM-3DP. Insert fabrication utilized biocompatible, biodegradable, bioadhesive Klucel™ hydroxypropyl cellulose polymer, subjected to distinct FDM-3DP processing parameters, utilizing a design of experiment approach to achieve a tailored release profile. We determined the drug content, thermal properties, drug-excipient compatibility, surface morphology, in vitro release, antibacterial activity, ex-vivo transcorneal permeation, and stability of inserts. An inverse relationship was noted between insert thickness, infill density, and drug release rate. The optimized design demonstrated an amorphous solid dispersion with an extended-release profile over 24 h, no physical or chemical incompatibility, excellent mucoadhesive strength, smooth surface, lack of bacterial growth (Pseudomonas aeruginosa) in all release samples, and prolonged transcorneal drug flux compared with commercial eye drops and immediate-release inserts. The designed inserts were stable at room temperature considering drug content, thermal behavior, and release profile over three months. Overall, the fabricated insert could reduce administration frequency to once-daily dosing, affording a promising topical delivery platform with prolonged antibacterial activity and superior therapeutic outcomes for managing ocular bacterial infections.

The effect of amniotic membrane proteins released by ocular inserts containing self‐healing hydrogels

AbstractPurpose: Growth factors found in the amniotic membrane (AM) help accelerate epithelium regeneration in the damaged cornea or conjunctiva. This study compares the effects of hydrogels releasing the AM proteins on the proliferation, migration, and time‐to‐closure (healing) of the conjunctival epithelium.Methods: Proteins extracted from the AM using sonication were incorporated into two hydrogels used as ocular inserts. The tested inserts materials were the self‐healing, dynamic hyaluronic‐acid hydrogel based on gold‐thiolate/disulfide exchange (Hydrogel A) and a physically cross‐linked hydrogel based on a combination between Eudragit S100 and hyaluronic acid with a reinforced matrix by polyvinyl alcohol, polyvinyl pyrrolidone and polyethylene glycol (Hydrogel B). In an in vitro experiment, a scratch was made on the human conjunctival epithelium cells (Chang Conjunctiva, Clone 1‐5c‐4) to mimic an incision wound. The cells were cultured with hydrogels for 48 hours to study the effect of these materials on epithelium repair. The samples were examined using a Zeiss Observer Z1 inverted microscope, and the results were evaluated employing the Image‐J program to obtain the cell migration rate (μm/h).Results: Hydrogel A increased the rate of closure at 22 h (121 ± 19 μm) in comparison with Hydrogel B (394 ± 78 μm). After 46 h, the scratches in Hydrogel A and control cultures were completely closed, while the Hydrogel B samples had an unclosed area of 54 ± 4 μm.Conclusions: Both hydrogels promoted wound healing in cultured conjunctival epithelium cells. However, a lower rate of wound closure was observed for Hydrogel B than for Hydrogel A and the control, probably because the speed of cell proliferation was slower in Hydrogel B. The wound‐healing assay showed that the Hydrogel A and B increased cell viability and significantly stimulated cell migration.

Formulation development and in Vitro–Ex vivo characterization of hot-melt extruded ciprofloxacin hydrochloride inserts for ocular applications: Part I

This study developed, optimized, characterized, and evaluated bioadhesive, hot-melt extruded (HME), extended-release ocular inserts containing ciprofloxacin hydrochloride (CIP-HCL) to improve the therapeutic outcomes of ocular bacterial infections. The inserts were fabricated with FDA-approved biocompatible, biodegradable, and bioadhesive polymers that were tuned in different ratios to achieve a sustained release profile. The results revealed an inverse relationship between the Klucel™ hydroxypropyl cellulose (HPC, 140,000 Da) concentration and drug release and extended-release profile over 24 h. The CIP-HCL-HME inserts presented stable drug content, thermal behavior, surface pH, and release profiles over three months of room-temperature storage and demonstrated adequate mucoadhesive strength. SEM micrographs revealed a smooth surface. Bacterial growth was not observed on the samples during the in vitro release experiment (0.5–24 h), indicating that a minimum inhibitory concentration (MIC) of 90 against Pseudomonas aeruginosa was achieved. Ex vivo transcorneal permeation studies using excised rabbit corneas revealed that the prepared ocular inserts prolonged the transcorneal flux of the drug compared to commercial eye drops and immediate-release inserts and could reduce the administration frequency to once daily. Therefore, the inserts could increase patient compliance and exhibited prolonged antibacterial activity and thus could provide better therapeutic outcomes against ocular bacterial infections.

OCULAR DRUG DELIVERY SYSTEMS: AN OVERVIEW

The treatment for the ophthalmic diseases are topical route because of the various ocular barrier. Ocular drug delivery systems are considered as major challenges by today’s pharmacologist and formulation scientist. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery techniques, which may surpass these barriers and maintain drug levels in tissues. There are many eye ailments which affected to eye and one can loss the eye sight also. Therefore, many ophthalmic drug delivery systems are available. These are classified as conventional and non- conventional (newer) drug delivery systems. Most commonly available ophthalmic preparations are eye drops and ointments about 70% of the eye dosage formulations in market. So overcome to these problems newer pharmaceutical ophthalmic formulation such as in-situ gel, nanoparticle, liposome, nanosuspension, microemulsion, intophoresis and ocular inserts have been developed in last three decades increase the bioavailability of the drug as a sustained and controlled manner.

An ocular insert with zero-order extended delivery: Release kinetics and mathematical models

Ocular inserts (InEye®), were prepared based on two distinct formulations of PCL-PEG-PCL block copolymers – one with 33 % and the other with 24 % of PEG 600. Ring-open-polymerisation was used to link ε-caprolactone monomers to PEG hydroxyl end-groups. Molecular weight, PCL/PEG ratio, mass loss and swelling of different polymeric samples where determined.Based on the previously prepared block copolymers, ophthalmic inserts were assembled. These were prepared with an ellipsoidal shape by dripping melted polymer over a micro-tablet of moxifloxacin, used as drug model for this study, which therefore became entrapped in a central core coated with a polymer layer that functioned as a control-release barrier.The release kinetics of the model drug revealed a strong dependence on the PEG percentage on the polymer. Inserts’ size and the amount of drug immobilized also had an important effect on the drug release profile. All release profiles followed a zero-order pattern, with 95 % of the drug being release at a constant rate.With drug releases varying from 20 to 200 days, and no initial burst, InEye® performance is unique among drug delivery systems and seems to be a very promising new formulation technology for preparing tailor-made ophthalmic inserts for prolonged and constant release of drug, which is needed for chronic diseases such as glaucoma, where compliance to treatment is essential for preventing optic-nerve lesions.

Formulation and evaluation of polymer-coated bimatoprost-chitosan matrix ocular inserts for sustained lowering of IOP in rabbits

Bimatoprost (BIM), a prostaglandin analog is a promising drug for treating glaucomic symptoms. However, Bimatoprost has short elimination half life in addition, the eye drops that are most prevalently sold on the market have a shorter ocular residence time; as a result, the drug has a poor bioavailability. The current study's goal was to create and test a promising sustained-release ocular insert for bimatoprost. By the solvent casting method BIM-chitosan matrix was prepared and the dried film was coated with Polycaprolactone (PCL)/PCL-PVA solution. Studies on swelling index, ATR-FTIR, drug content uniformity were used to characterise the inserts. SEM was used to observe surface morphology of uncoated insert, and PCL and PVP K 30 coated inserts. And thickness of the ocular insert (51 μm). In vitro studies were carried out using Franz diffusion cells. In vivo studies were conducted on healthy rabbits to examine changes in intraocular pressure (IOP), showed IOP of 15.9 mmHg for BIM-PCL insert and 14.6 mmHg for BIM-PVP insert at 120 h. This confirmed that the BIM inserts were able to have sustained reduction of IOP for a period of six days.

Electrospun Nanofiber Composite for Levofloxacin in Ocular Drug Delivery

Background: Levofloxacin is available in the form of an eye drop solution for the treatment of ocular bacterial infection and inflammatory diseases. Below 5% of the drug gets absorbed after topical application of eye drop. The major portion of administered drug either comes out from the eye or drains out by the nasolacrimal duct, which results in poor bioavailability. Objective: We aim to prepare a polymeric ocular insert containing levofloxacin as a drug prepared by the electrospinning technique that can release the drug for an extended duration. Methods: Electrospun nanofiber sheets were prepared using hydroxypropyl cellulose and polycaprolactone polymer. Drug content was analysed by HPLC. Nanosheet was examined by DSC and FTIR for compatibility study. Optimized nanosheet was further studied for weight uniformity, swellability index, surface pH, and in-vitro drug release. The morphology of the prepared sheets was examined using optical microscopy and SEM analysis. Results: The uniform, beadles, and continuous nanofibers were obtained by electrospinning. From the DSC and FTIR data, it was proved that drugs and polymers were compatible in nanosheets. Drug content and % drug loading in the electrospun sheets were found to be 101.70% and 4.33%, respectively. The thickness of the sheets was around 0.31± 0.04 mm and the swelling index was observed at 566.66% after 30 min. The surface pH of the ocular insert was found to be 6.81 and 6.83 after 30 min and 24 h., respectively. In-vitro drug release showed that 99% of the drug was released in 24 h Conclusion: A prepared nanocomposite sheet can be used for the sustained drug delivery of levofloxacin in ocular eye disease, reducing the dosing frequency and improving patient compliance.

Eudragit® L100/Polyvinyl Alcohol Nanoparticles Impregnated Mucoadhesive Films as Ocular Inserts for Controlled Delivery of Erythromycin: Development, Characterization and In Vivo Evaluation.

The fast elimination of drugs from the cornea is one of many challenges associated with the topical administration of conventional dosage forms. The present manuscript aimed to prepare modified-release inserts containing erythromycin (ERY) to enhance drug delivery and address the aforementioned limitation. Film formulations were developed using Eudragit® L100 (EUD) and Polyvinyl Alcohol (PVA) polymers. ERY-loaded EUD-based nanoparticles were developed by the colloidal dispersion method using PVA as the emulsifier. The film-casting method was applied to form the mucoadhesive films using sodium alginate, gelatin, cyclodextrin-α, and β as polymeric film matrices. Different physicochemical properties of the optimized formulations and in vitro release profiles were evaluated. The in vivo evaluation was performed by collecting tear samples of rabbits using a novel, non-invasive method following the administration of inserts in the cul-de-sac. The ERY amount was assayed using a microbiological assay. The developed films showed prolonged in vitro and in vivo release profiles over five to six days; they had suitable physicochemical properties and a tensile strength of 2–3 MPa. All formulations exhibited antibacterial efficacy against E. coli and S. aureus with more than 20 mm diameter of inhibited growth zones. None of the formulations caused irritation to the rabbit’s eye. The inserts showed promising pharmacokinetics with AUC0–120 of 30,000–36,000 µg·h/mL, a Cmax of more than 1800 µg/mL at 4 h, and maintained drug concentration over the threshold of 5 µg/mL during the following 120 h of study. Nanoparticle-containing, mucoadhesive films could be fabricated as ocular inserts and can prolong the topical ocular delivery of ERY.

ИЗУЧЕНИЕ ВЛИЯНИЯ ВСПОМОГАТЕЛЬНЫХ ВЕЩЕСТВ НА БИОФАРМАЦЕВТИЧЕСКИЕ ПОКАЗАТЕЛИ ЛЕКАРСТВЕННОЙ ФОРМЫ «ГЛАЗНЫЕ ПЛЁНКИ»

Abstract. The spread of ophthalmic infectious diseases around the world and uniformity of the market of dosage forms for their therapy generate an incentive for scientists to develop innovative drug forms, to create improved therapy for such diseases as uevitis, conjunctivitis, keratitis and blepharitis. There are two types of eye dosage forms on the market of the Russian Federation - drops and ointments, which have a short shelf life after the first application, a high risk of microbial infection and infection of a "healthy" eye. Based on these facts, the study aims to develop a solid extended dosed biodegradable ocular insert for use in ophthalmotherapy. This article is devoted to the peculiarities of influence of film forming agents of different nature, plasticizer and solubilizing agent (poloxamer) and their ratio on the biopharmaceutical properties of the polymeric base of ocular insert. Polymers of both natural and semi-synthetic nature (hydroxyethylcellulose, sodium alginate, xanthan and gellan gum) were used to create the polymeric basis. Placebo inserts were formed at room temperature in open space for three days. The test of the samples was carried out according to the parameters of description, elasticity, dissolution time, humidity, which include in the State Pharmacopeia XIV, and mucohedhesion, that is an important parameter for locally administering on mucosa, although it is not regulated in official documents. The series of experiments showed the optimum concentrations and ratios of the auxiliary substances used, namely 0.5% to 2.5% for film type manufacturers, 2% for plasticizers and 0.5% for poloxamers, respectively. The formulations that showed the best performance when evaluating the parameters were - sodium alginate 2.5%, glycerin 2%, poloxamer 0.5%, water purified up to 40.0; xanthan gum 0.4%, glycerin 2%, poloxamer 0.5%, water purified up to 40.0.have a wide variation in different age categories, which requires further study. on additional samples of children in the region.

Nanosuspension as Promising and Potential Drug Delivery: A Review

In the last decade, nanosuspensions have gained considerable interest as a method for formulating poorly soluble drugs. Because of their cost-effectiveness and technological simplicity compared to liposomes and other colloidal drug carriers, nanoscale systems have recently received a lot of attention as a way of solving problems of solubility. Nanosuspensions are biphasic systems comprising of pure drug particles dispersed in an aqueous vehicle, stabilized by surface active agents. Fabrication of nanosuspension is simple and more advantageous than other approaches. Nanosuspension is a very finely single solid drug particle in an aqueous vessel, stabilized by surfactants for either oral or topical use or for parenteral and pulmonary administration, it can also be used for targeted drug delivery when incorporated in the ocular inserts and mucoadhesive hydrogels, with reduced particle size resulting in increased dissolution rate. This article covers the preparation of nanosuspension by bottom up technology, top down technology, melt emulsification, emulsification- solvent evaporation and supercritical fluid with their advantages and disadvantages, aspects of structure, classification and their drug delivery applications. Nanosuspension can be processed for the drugs which are of hydrophobic in nature quite easily employing stability enhancers, solvents that are of organic and additional ingredients including buffering agents, salts, PEG, osmotic agents and anti-freeze compounds.

Dexamethasone Loaded Electrospun Nanocomposite Ocular Insert: In-vitro Drug Release and Mechanical Assessment

Background: Dexamethasone is currently available as suspension for the treatment of anterior ocular inflammatory diseases that are given through eye drops. Upon topical delivery by eye-drops, less than 5% of the drug gets absorbed when applied topically as eye drops. The major portion of administered drug either comes out from the eye or gets subjected to nasolacrimal drainage resulting in poor bioavailability. Objective: The present study is aimed at developing polymeric ocular insert containing dexamethasone as a drug by employing the use of electrospinning technique. Methods: Dexamethasone (0.1% w/v) loaded electrospun sheet was also made using 10% w/v EC: HPMC: PEO (60:20:20) in solvent system of ethanol: water (90:10) at optimized electrospinning parameters of 12kV with a flow rate of 0.8mL/hr and distance of 20 cm between tip and collector. Results: The prepared nanocomposite insert was characterized for DSC and FTIR-ATR spectroscopy revealing no physical-chemical interaction between drug with polymers. The thickness of the electrospun sheet was found to be 270±0.02 μm and % drug content was found to be 0.43±0.01% w/w. The release profile showed that around 95% drug was released in 48 hrs. This release profile showed the prepared drug-loaded electrospun ocular insert was best suitable for once-a-day delivery. Assessment of mechanical properties like young’s modulus, tensile strength, and % elongation showed that the prepared insert can be handled easily without any breakage or damage. Conclusion: Upon delivery in conjunctival sac, this is best suitable for once-a-day delivery. The developed electrospun insert, consisting of a unique polymer composite of biodegradable polymers, avails the benefits of nanofibers imparting prolonged release and this novel formulation overcomes the limitations of conventional therapies. This reduces the dosing frequency and improves patient compliance.

Sustained Release Biocompatible Ocular Insert Using Hot Melt Extrusion Technology: Fabrication and in-vivo evaluation

Topical eye drops usually have low bioavailability of the drug. Rapid turnover of lacrimal fluid flushes the drug away from the ocular surface, and the drug has limited time for absorption. Therefore, we design Metoprolol loaded ocular insert to enhance bioavailability against glaucoma in this study. Hot-melt extrusion was utilized to prepare the inserts using Gelatin, GelMa, and Polyacrylic acid (PAA) as matrix-forming polymers. The prepared ocular insert was characterized for physicochemical properties and in vitro drug release. It was observed that GelMa concentration and PAA concentration greatly affected drug release. Inserts prepared from Gelatin-PAA released 38.6% Metoprolol in the first hour. However, replacing 20% of Gelatin with GelMa reduced the initial release to 23.6%.Moreover, inserts prepared with 30% GelMa released 19% of the drug in the first hour, which exhibited a quasi zero-order release profile. The effect of PAA concentration on the release of the drug was also very evident. Inserts prepared with 5% PAA concentration released around 30% of the drug in the first hour, while those prepared with 20% PAA took 2 h to release a similar amount of drug. Similarly, 81% and 50% of the drug were released after 4 h from inserts containing 5% PAA and 20% PAA, respectively. Thus, it is clear that Metoprolol release can be tuned by varying the GelMa and PAA concentration in the formulation. The insert, which was able to sustain the drug release for 12 h, has the potential to be used as a good ocular delivery system, which requires less frequent dosing compared to eye drops.