Ocular Inserts Research Articles

Formulation, in vitro and in vivo evaluation of lidocaine HCl ocular inserts for topical ocular anesthesia

Topical anesthesia is a safe and cost-effective method considered as the first-choice in many procedures. The objective of the present study was to develop ocular inserts as a new form of lidocaine HCl to give a sufficient level of anesthetic. Ocuserts were prepared using HPMC and PVA in different ratios with lidocaine HCl alone and lidocaine HCl β-cyclodextrins complex. Drug polymer interactions were studied by Fourier transform infrared spectroscopic studies. The prepared ocular inserts were characterized by means of ocusert thickness, weight variation, folding endurance, surface pH, moisture absorption, drug content and in-vitro drug release. Stability study was conducted on selected formulations, and in vivo evaluation of lidocaine HCl was also carried out. The results revealed that F7 formulations containing drug β-cyclodextrins with 4 % HPMC and 2 % PVA were found to have good physical characteristics and appropriate flexibility. In addition to the highest initial and cumulative percentage of drug released in vitro. The selected F7 ocuserts retained their characteristics during the stability study. The results of in vivo study showed that the addition of β-cyclodextrins in F7 significantly increase the drug content in the aqueous humor when compared with F3 ocuserts containing lidocaine HCl alone.

Design, formulation, and evaluation of novel sustain release bioadhesive in-situ gelling ocular inserts of ketorolac tromethamine.

Introduction:The eye is an interesting organ. The tear flow and blinking reflex maintains a good environment and removes foreign material from the eye. Several polymeric systems have been used to fabricate ocular inserts for better ocular bioavailability and retention to drug of which gelling systems have shown advantages of convenient administration and increased contact time.Aim:The purpose of the present study was to develop a bioadhesive in-situ gelling ocular insert of Ketorolac tromethamine using polymeric system of sodium alginate as gelling and chitosan as bioadhesive agent.Methods:Various batches of ketorolac tromethamine bioadhesive in-situ gelling ocular inserts were prepared using sodium alginate and chitosan with glycerin as a plasticizer by solvent casting method. The formulated bioadhesive in-situ gelling ocular insert were then evaluated for physical appearance, thickness, weight variation, folding endurance, percentage moisture loss, percentage moisture absorption, tensile strength, percentage flatness, bioadhesive strength, force of adhesive, drug content, in vitro drug release, sterility test, in vitro antimicrobial efficacy, and stability study.Results:The formulation F4 was shown 98.62 % drug release at the end of 12 h. Hence that F4 formulation was maximum sustain drug release than other formulation and also optimum and better result of physicochemical properties than other formulation. This optimized formulation was subjected to sterility and stability test. There was no evidence of microbial growth and hence the ocular insert passed the sterility test and there was no significant change in the physicochemical properties from 0th to 30th day. Hence, the formulation was found to be stable.Conclusion:The said promising formulation (F4) would be able to offer benefits such as increase residence time, prolonged drug release, reduction in frequency of administration and thereby definitely prove to improve the patient compliance.

Bilayered Films Based on Novel Polymer Derivative for Improved Ocular Therapy of Gatifloxacin

Context. Thiomers could prove to be suitable mucoadhesives for fabrication of ocular inserts. Objective. The study intends to explore the application of thiolated sodium alginate (TSA) to the preparation of bilayered ocular inserts of gatifloxacin. Methods. Cysteine moieties were grafted onto sodium alginate (SA) and the resultant thiomer was characterized for relevant physicochemical properties. Bilayered inserts were fabricated with a mucoadhesive immediate release layer composed of either SA or TSA and a sustained release layer composed of acrylates. Films were prepared by solvent evaporation and evaluated for mechanical properties, drug content, and in vitro release. Results and Discussion. The synthesized TSA possessed 248.80 ± 49.7 μmol thiol groups/gm and its solutions thickened on standing due to disulphide bridging. Its films showed improved mucoadhesion and also a strikingly beneficial property of resisting erosion and remaining as a hydrated adhesive layer for the duration of drug release. The bilayered films were found to be flexible, with good folding endurance, uniform thickness, and appropriate drug content, and showed a release of about 80% of loaded gatifloxacin in 12 h. Conclusion. The study demonstrates promise in employing thiolated polymer in conjunction with acrylates for the design of ocular inserts for twice a day therapy with gatifloxacin.

Current nanotechnological strategies for treating glaucoma.

Glaucoma is a common cause of blindness worldwide, and the development of treatments is difficult for pharmaceutical scientists because successful delivery of drugs to the anterior and posterior segments of eye is challenging due to anatomical and physiological constraints. Conventional treatments use various dosage forms (solutions, suspensions, and ointments) that are hindered by poor intraocular penetration and/or rapid ocular elimination. Therefore, effective, safe, and comfortable methods of drug delivery are needed. One approach to improving ocular therapy is the use of nanotechnology for drug delivery. Recent drug delivery approaches using gels, liposomes, niosomes, ocular inserts, contact lenses, microparticles, nanoparticles, nanosuspensions, and other materials have produced exciting new therapies for ocular diseases, especially glaucoma. In this review, we discuss the importance of nanotechnology in novel drug delivery systems and the future possibilities for an effective treatment of glaucoma.

Chick chorioallantoic membrane model for in ovo evaluation of timolol maleate–brimonidine tartrate ocular inserts

The main aspire of this study was to develop ocular drug delivery system for dual drug glaucoma therapy by timolol maleate–brimonidine tartrate and endeavor the possibility of biocompatibility studies by in ova studies. Matrix type, both hydrophilic and lipophilic polymers, and reservoir-type ocular inserts of timolol maleate were prepared using hydrophilic polymers like polyvinyl alcohol, hydroxyl propyl methyl cellulose K4M and lipophilic polymers like ethylcellulose and eudragit S100 and were optimized. Based on the optimized formulation, triple-layered ocular inserts (reservoir type) of dual drug were prepared by solvent casting technique with an objective of reducing the frequency of administration, obtaining controlled release and greater therapeutic efficacy, preservative free dosage form for the treatment of glaucoma. FTIR spectral studies revealed no pharmaceutical incompatibility and no drug polymer interactions. Maximum drug release (99.18 ± 1.7) was achieved when PVP and HPMC K4M in 1:1 ratio with PEG 400 (0.3 ml) drug reservoir layer was sandwiched between ethyl cellulose as rate control membrane up to 32 h in a controlled fashion. Drug release was by non-Fickian diffusion mechanism for single drug formulation. But in dual drug insert, timolol maleate best fit into zero order and for brimonidine tartrate to Higuchi model and diffusion of drugs from this by non-Fickian diffusion mechanism. In ovo studies suggested that the optimized formulation was found to be sterile, biocompatible and physicochemically stable and support us to claim that the developed formulation was biocompatible.

In vitro characterization of a controlled-release ocular insert for delivery of brimonidine tartrate

Glaucoma is the second leading cause of blindness in the US. Brimonidine tartrate (BT) is a modern anti-glaucoma agent that is currently administered as frequently as a thrice-daily topical eye drop medication. Accordingly, compliance with BT regimens is low, limiting overall effectiveness. One attempt that has previously proved effective in addressing non-adherence is the formation of ocular inserts, such as the Ocusert®, whose diffusion-based control released an older drug (pilocarpine) for a week-long period. Modern controlled drug-release technology provides an avenue for extending the release of practically any drug (including new drugs such as BT) for as long as 1month from a singular insert. Currently, no controlled-release formulations for BT exist. This work outlines the development and characterization of a BT-releasing ocular insert designed from poly(lactic co-glycolic) acid/polyethylene glycol (PEG). It was found that a formulation containing 15% PEG can be created that produces a linear BT-release profile corresponding to BT eye drop delivery estimates. Additionally, these inserts were shown, through the use of atomic force microscopy and scanning electron microscopy, to have smooth surfaces and physical properties suitable for ophthalmic use.

Long Acting Betaxolol Ocular Inserts based on Polymer Composite

Poor bioavailability and therapeutic response of conventional therapy due to many pre-corneal constraints necessitate the development of novel controlled and sustained ocular drug delivery to become a standard one in modern pharmaceutical era. This investigation aimed to study the drug release kinetics of betaxolol hydrochloride from a hydrophobic matrix system of PMMA cast with incorporating different proportions of polyethylene oxide (PEO) and evaluate its ability to improve ocular bioavailability and duration of action for the drug. Matrix type ocular inserts were prepared by the film casting technique and characterized in vitro by drug release studies using a flow through apparatus that simulated the eye conditions. All the formulations were subjected to physicochemical evaluation. Rabbit model with steroid induced glaucoma was used to establish in vivo efficacy of inserts. Polymer composition and concentration significantly affected the drug release based on change in diffusional path length and formation of gelaneous pores by polymer erosion. Formulations released the drug by non-fickian diffusion including anomalous transport (0.5<n<1) and super case II transport (n>1). It was also observed that increasing the proportion of PEO in to PMMA does not affect the blend miscibility. IVIVC suggested no significant difference (P< 0.001) between in vitro and in vivo release of drug from inserts. In vivo IOP lowering activity was better for optimized insert F8 (for 24 h) as compared to eye drops (10 h). This ocular insert could be a promising once-a-day sustained release formulation for treating glaucoma.

Design and evaluation of esmolol hydrochloride ocular inserts with special reference to glaucoma treatment

In developing a drug delivery strategy, issues of absorption, distribution, metabolism, and elimination must be considered. The eye presents unique opportunities and challenges when it comes to the delivery of pharmaceuticals. While absorption by this route is bungling, there are few side effects with conventional ocular dosage forms. Hence, ocular inserts were prepared with prolonged release of drug and minimum swelling within cul-de-sac using esmolol HCl drug the work focuses on treatment of glaucoma by formulating ocular inserts. By using different polymeric combination of esmolol HCl using hydroxypropyl methyl cellulose (HPMC 3–5 %), chitosan (3–5 %), polyvinyl alcohol (PVA 3–5 %), methyl cellulose (3–5 %) as polymer by solvent casting technique with objective of increasing contact time, achieving controlled release, reduction on frequency of administration and greater therapeutic efficiency. The prepared ocular insert were then evaluated for physical appearances tensile strength, % elongation at break, stress, weight variation, uniformity of thickness, % moisture absorption, surface pH, folding endurance, Fourier transform infrared spectroscopy, in-vitro transcorneal permeation studies etc. It is evident from these study that formed polymeric ocular insert have appreciable strength and safety. Physicochemical characterization and in vitro transcorneal permeation studies revels that, the prepared ocular insert formulation F2 and F8 containing HPMC and PVA had release their drug content, 98.54 and 97.24 respectively over a extended period of 24 h. Hence these formulation selected as best optimized formulation.

MICROSPHERES AS AN OCULAR DRUG DELIVERY SYSTEM- A REVIEW

Ophthalmic drug delivery is most interesting and challenging delivery system facing the pharmaceutical scientist. The anatomy, physiology, and biochemistry of the eye render this organ highly impervious to foreign substances. A significant challenge to the formulator is to circumvent the protective barriers of the eye without causing permanent tissue damage. These barriers affect the bioavailability of drugs. Development of newer, more sensitive diagnostic techniques and novel therapeutic agents continue to provide ocular delivery systems with high therapeutic efficacy. These includes iontophoresis, liposome bioadhesive gels, ocular insert, contact lenses, liposomes & a special one is microspheres. Microsphere is a well designed controlled drug delivery system can overcome some of the problems of conventional therapy and enhance the therapeutic efficacy of a given drug. This approach delivering a therapeutic substance to the target site in a sustained controlled release fashion & achive a good bioavalability in ocular delivery system.

Use of a New Ocular Insert versus Conventional Mydriasis in Cataract Surgery

Background. To compare the efficacy and safety of a new ocular insert versus conventional mydriasis in cataract surgery. Methods. We selected 70 patients undergoing cataract surgery. Thirty five patients (Group 1) received instillation of mydriatic drops (tropicamide 1%, phenylephrine 10%, and cyclopentolate 1%) prior to surgery, and 35 patients (Group 2) had a Mydriasert insert (Théa Pharma) (0.28 mg of tropicamide and 5.4 mg of phenylephrine hydrochloride) placed in the inferior fornix. Pupil size before and after surgery, blood pressure, and heart rate were measured. Results. Before surgery, pupil diameter was 9.44 ± 1.17 mm in Group 1 and 9.05 ± 1.54 in Group 2 (P > 0.05). Twenty four hours after surgery, pupil diameter was 5.20 ± 1.54 mm in Group 1 and 3.33 ± 1.15 in Group 2 (P < 0.001). There were no statistically significant differences in blood pressure or heart rate between groups. Conclusions. The effect of the Mydriasert insert was similar to conventional mydriatic agents. Pupil size was restored to normal faster when using the Mydriasert insert compared with conventional mydriatic agents for pupil dilation.

Design and evaluation of aceclofenac ocular inserts with special reference to cataracts and conjunctivitis

Design and evaluation of aceclofenac ocular inserts with special reference to cataracts and conjunctivitis

Safety and accuracy of a new long‐term subconjunctival glucose sensor

A new biosensor has been developed by EyeSense (Großostheim, Germany) that is placed into the conjunctiva of one eye to measure the glucose concentration of the surrounding tissue in a non-invasive manner. In the present study we investigated the correlation between glucose concentrations measured by the EyeSense implant and those determined by finger prick testing, as well as the tolerability and safety of the implant over a 16-week period. The study was performed in 28 diabetic patients. The biosensor was inserted under local anesthesia and sterile conditions. Correlations between capillary glucose measured by laboratory methods and interstitial glucose determined by the biosensor were investigated by inducing increases and decreases in glucose values between 60 and 300 mg/dL. Most patients experienced a mild subconjunctival hemorrhage postoperatively. Except for the minor sensation of the presence of foreign body, the implants were well tolerated. Three patients lost the ocular mini insert spontaneously, whereas there was a function failure of the insert in four patients. Error grid analysis showed that the percentage of data pairs in the acceptable ranges (zone A and B) was very high (>96%). However, there was a shift from zone A to zone B during observation. This was due primarily to an increase in the lag time between capillary and interstitial measured glucose. he present study demonstrates good tolerability and measurement performance of the biosensor. The reasons for an increase in the lag time are still unknown; local reactions may be involved.

COMPARATIVE EVALUATION OF POLYMER COMBINATION IN THE DESIGN OF BRIMONIDINE TARTRATE OCULAR INSERTS

Brimonidine is an anti-glaucoma agent useful in treatment of intraocular pressure. In the present study an attempt was made to formulate ophthalmic inserts of brimonidine tartrate (BT) in combination with polymers like methylcellulose, carboxymethyl chitosan and HPMC. Prepared ocular films were evaluated for uniformity in thickness, weight variation, % moisture absorption, % moisture loss, in vitro and in vivo release studies. The physical characteristics of the films were found to be within acceptable limits. The study confirmed that brimonidine tartrate can be delivered through films made of methyl cellulose, carboxymethyl chitosan and HPMC combination matrix cast with ethyl cellulose (EC). In vitro release study revealed that increasing the proportion of polymer concentration decreased the rate of release of brimonidine tartrate. In vivo release profile of ocular inserts revealed controlled release of drug over a period of 24 h. Optimized formulation CH3 was evaluated for in vivo release characteristics using rabbits as animal model. The optimized formulation CH3 was found to be stable at accelerated storage condition of 40/75 % RH.

Challenges in Neuroprotective Nanomedicine Development: Progress Towards Noninvasive Gene Therapy of Glaucoma

Over the past decade the application of gene therapy of retinal diseases such as glaucoma has produced promising results. However, optic nerve regeneration and restoration of vision in patients with glaucoma is still far from reality. Neuroprotective approaches in the form of gene therapy may provide significant advantages, but are still limited by many factors both at the organ and cellular levels. In general, gene delivery systems for eye diseases range from simple eye drops and ointments to more advanced bio- and nanotechnology-based systems such as muco-adhesive systems, polymers, liposomes and ocular inserts. Most of these technologies were developed for front-of-the-eye ophthalmic therapies and are not applicable as back-of-the-eye delivery systems. Currently, only the invasive intravitreal injections are capable of successfully delivering genes to the retina. Here we review the challenges and possible strategies for the noninvasive gene therapy of glaucoma including the barriers in the eye and in neural cells, and present a cross-sectional view of gene delivery as it pertains to the prevention and treatment of glaucoma.

PROMISING IMPLICATION OF OCUSERTS IN OCULAR DISEASE

Ocular route of drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist. The anatomy, physiology and biochemistry of the eye render this organ exquisitely impervious to foreign substances. The challenge to the formulator is to circumvent the protective barriers of the eye without causing permanent tissue damage In spite of extensive pharmacological and clinical data pointing to the usefulness and advantages of solid devices for topical drug delivery to the eye, liquid, and to a smaller extent, gel-type preparations appear to enjoy the continued interest of manufacturers and ophthalmologists. The main purpose of preparing ocular insert is to increase ocular bioavailability of drug. Ocular inserts maintain the drug concentration within a desired range. Fewer administrations are required so they increase patient compliance. In the present update, the advantages, disadvantages and requirement for success of ocular inserts, and examine the few inserts which are available on the market or are being developed by pharmaceutical companies for drug delivery. In this review, we have focused on the present era of ocuserts helps in treating eye diseases. Â

Design and evaluation of moxifloxacin hydrochloride ocular inserts

The objective of the present investigation was to prepare and evaluate ocular inserts of moxifloxacin. An ocular insert was made from an aqueous dispersion of moxifloxacin, sodium alginate, polyvinyl alcohol, and dibutyl phthalate by the film casting method. The ocular insert (5.5 mm diameter) was cross-linked by CaCl2 and was coated with Eudragit S-100, RL-100, RS-100, E-100 or L-100. The in vitro drug drainage/permeation studies were carried out using an all-glass modified Franz diffusion cell. The drug concentration and mucoadhesion time of the ocular insert were found satisfactory. Cross-linking and coating with polymers extended the drainage from inserts. The cross-linked ocular insert coated with Eudragit RL-100 showed maximum drug permeation compared to other formulations.

DESIGN AND EVALUATION OF POLYMERIC OCULAR DRUG DELIVERY SYSTEM FOR CONTROLLED DELIVERY OF CIPROFLOXACIN HYDROCHLORIDE

The field of Ocular drug delivery is one of the interesting and challenging endeavors facing the pharmaceutical scientist. The most frequently used dosage forms i.e. ophthalmic solutions and suspensions are compromised in their effectiveness by several limitations, leading poor ocular bioavailability. Ocuserts (or) Ophthalmic inserts are sterile preparations containing drug as dispersion or as solution in the polymeric support. Ocusert helps to improve ocular bioavailability by increasing the duration of contact with corneal tissue, thereby reducing the frequency of administration. Ciprofloxacin is a fluoroquinolone antibacterial drug effective in the treatment of bacterial conjunctivitis. The ciprofloxacin hydrochloride ocuserts were then evaluated for their physicochemical parameters like uniformity of thickness, weight, drug content and in vitro release pattern. It can be concluded that this ocular inserts formulation can be a promising for controlled release formulation. Keywords: Ocusert, Ciprofloxacin hydrochloride, In vitro release pattern, controlled release.

Ocular insert for sustained delivery of gatifloxacin sesquihydrate: Preparation and evaluations

Background:Many polymeric systems have been used to fabricate ocular inserts for improve ocular bioavailability and retention to drug of which matrix systems have shown advantages of reduce dosing frequency and increased corneal residence time. The objective of the present investigation was to prepare and evaluate ocular inserts of gatifloxacin.Materials and Methods:Ocular insert was made from an aqueous dispersion of gatifloxacin, sodium alginate, polyvinyl alcohol, and glycerin by solvent casting method. Ocular insert (5.5 mm) was cross-linked by CaCl2 and was coated with Eudragit RL-100 or Eudragit RS-100. The ocular inserts were characterized for thickness; uniformity of weight, drug content uniformity, % moisture absorption or moisture loss, and surface pH. The in vitro diffusion studies were carried out by putting insert on Millipore membrane filter (0.8 μm) fixed between donor and receptor compartment of an all glass modified Franz diffusion cell.Results:The thickness and drug content of ocular insert were found in the range of 0.11 ± 0.003 to 0.24 ± 0.010 mm and 0.718 ± 0.002 to 0.867 ± 0.007 mg, respectively. The surface pH, % moisture absorption or moisture loss and weight variation values were obtained in satisfactory range. The cross-linked ocular insert coated with Eudragit RL-100 shows maximum drug permeation i.e. 89.53 % ± 0.43 at 11 h. The stability studies suggest that all ocular insert remained stable, showed lesser degradation rate and maximum shelf life.Conclusion:Ocular inserts of gatifloxacin were prepared successfully by using solvent casting method for sustained drug delivery. The cross-linked and Eudragit RL-100 coated ocular insert of gatifloxacin provides better in vitro drug release and sustained upto 11 h.

Formulation and evaluation of controlled release ocular inserts of betaxolol hydrochloride

–Betaxolol Hydrochloride is a cardio selective β1 adrenergic receptor blocking agent used in the treatment of chronic open angle glaucoma and ocular hypertension In the present study, an attempt was made to formulate Betaxolol HCl ocular inserts. In matrix type the formulations for Betaxolol containing 10%, 12%, and 14% w/v of Gelatin, 1%, 1.5%, 2%, 2.5% and 3% w/v for Chitosan were prepared by solvent casting method and plasticizer were used in different concentration for smoothing texture of the ocular inserts. The prepared batches of ocular inserts were evaluated for weight variation thickness, drug content uniformity, swelling index. An increase in average weight and thickness is due to increase in polymer concentration. IR spectral studies were performed to confirm the interaction of drug with excipients. All formulations were tested for in vitro drug release (Simulated tear fluid) by vial method. The formulations GH8 and C5 show a maximum cumulative percentage drug release of 98.76% and 97.72% at the end of 12 th hrs, respectively. The drug release in all formulations decreases as the polymer concentration increases. The dissolution data of formulation were subjected to first order, Higuchi’s, and peppas equations. Drug release from the ocuserts by diffusion controlled mechanism. No significant change in the drug content and physical features was observed during storage at 25 0 C/60% RH and 40 0 C/75% RH for the selected formulation for three months. Keywords––Betaxolol Hydrochloride, Chitosan, Gelatin, Ocular inserts.

Design and evaluation of guar gum-based ofloxacin sustained release ocular insert

To prepare ocular inserts of ofloxacin using guar gum as a polymer for sustained delivery over a period of 24 h.Ofloxacin ocular inserts were prepared by the solvent casting method using guar gum in different proportions (0.5% w/v, 0.75% w/v and 1.0% w/v). The prepared formulations were evaluated for thickness, weight variation, percentage drug content, surface pH, folding endurance, percentage moisture absorption and loss, percentage swelling, mechanical strength and in vitro transcorneal permeation. In vitro transcorneal permeation study was performed on goat cornea using a modified Franz diffusion cell. The inserts were found to be of uniform thickness (ranging from 51.230 ± 0.385 μm to 109.275 ± 0.522 μm) and weight (1.720 ± 0.079 mg to 3.402 ± 0.105 mg). The % drug content in the inserts was found to vary between 95.450 ± 0.427% and 98.471 ± 0.225.The cumulative % drug releases from the formulation ranged from 38.19 to 75.21 over a period of 24 h. All the formulations followed a zero order release pattern. The in vitro transcorneal study revealed that an increase in concentration of the polymer slowed down the release of ofloxacin from the formulation.Ocular inserts using guar gum as a polymer were successfully prepared and can be effectively used for sustained ocular delivery over a period of 24 h.