Eye Drop Solution Research Articles

Stability of voriconazole 10 mg/mL ophthalmic solution during 90 days

Abstract Objectives Fungal keratitis is a rare but severe cause of infectious keratitis and can lead to blindness. To cure fungal keratitis, antifungal like voriconazole eye drops must be immediately administered. As no brand is available on the market, voriconazole ophthalmic solution is compounded in hospital pharmacies using voriconazole powder for intravenous infusion. The aims of our study were to both assess the physico-chemical and microbiological stability of eye drop solutions stored at +2 to 8 °C. Two different High-Density-Polyethylene (HDPE) eye drop dispensing containers were assessed, one with a sterility preserving cap Novelia®(Nemera) and the other without sterility preserving cap both provided by CAT laboratory. In addition microbiological quality was assessed during 15 days simulated patient use. Methods Multiple batches of voriconazole 10 mg/mL eye drops were prepared and stored at +2 to 8 °C to study their stability over 90 days. All analyses were performed in triplicate. Physical stability was determined, pH determination, osmolarity measurement, and a particle count test was also performed. A high performance liquid chromatography (HPLC-UV) stability indicating method was used to determine chemical stability of the ophthalmic solution over 90 days of storage. For microbiological stability, a sterility test was performed using closed membrane filtration method (Steritest®, Merck Millipore) at D0, D90 and D90+15 days after simulated administration of eye drops (D90+15). Results For both containers, no variation of visual aspect, pH, osmolality, particle count and final concentration were observed. No microbiological growth was observed after 90 days of storage. At the end of the simulated administration period (D+15), unconstant microbiological growth was only observed in HDPE vials without sterility preserving cap, whereas HDPE vials with a sterility preserving cap Novelia®(Nemera) remained sterile. Conclusions Voriconazole 10 mg/mL ophtalmic solution was stable during 90 days at +2 to 8 °C in lightproof HDPE vials without sterility preserving cap and HDPE vials with a sterility preserving cap Novelia®(Nemera). However, vials with classical cap which are not airtight systems, may microbiologically contaminated during patient’s use than vials with Novelia® cap thanks to their innovative valve system.

Timolol-eluting graphene oxide laden silicone contact lens: Control release profile with improved critical lens properties

Glaucoma is a chronic ocular disease characterized by increase in intraocular pressure (IOP). Currently, it is managed by high drug concentration eye drop solutions. The dosage form present <5% ocular bioavailability, due to ocular static and dynamic barriers. Ocular drug delivery using contact lens can ameliorate the disadvantages of conventional eye drop treatment. However, drug loading by traditional method using drug-packaging solution showed low drug uptake, burst released with altered swelling and optical properties. The direct drug loading method during lens fabrication show high drug loss during mandatory extraction and sterilization steps. Graphene oxide (GO), a single monomolecular layer nano-sheets, exhibit high drug loading capacity for hydrophobic drugs due to its π-conjugated stratum. In the present study, GO was incorporated into the contact lenses during fabrication step, to control the release profile of timolol along with improvement in opto-physical properties. These GO-laden contact lenses (SM-GO-TB) as well as blank contact lenses (SM-TB) were soaked in the solution of timolol. Alternatively, direct timolol-GO-lenses (DL-TB-GO) and direct timolol-lenses (DL-TB) were fabricated by adding timolol-GO and timolol during polymerization, respectively. GO improved the swelling of both soaked and direct laden contact lenses due to formation of hydrogen bounds between GO and water molecules. A significant improvement in the transmittance of GO-laden contact lenses was observed because of molecular dispersion of drug on the surface of GO. The addition of GO in the soaked and direct timolol-laden contact lenses showed significant decrease in burst release and improvement in the release profiles compared to respective contact lenses without GO. Thus, the study demonstrated that GO-laden contact lenses could improve the critical lens properties like swelling and transmittance with controlled release of timolol.

Spanlastics nanovesicular ocular insert as a novel ocular delivery of travoprost: optimization using Box–Behnken design and in vivo evaluation

Currently, travoprost is a synthetic prostaglandin F2α analogue used in the treatment of glaucoma, it is delivered by eye drop solution. Due to its very low bioavailability and patient non-compliance, the objective of the current study was to enhance its bioavailability, and prolong its release Spanlastic nano-vesicles gels were designed and optimized using Box-Behnken design. The optimized spanlastic nano-vesicles gel exhibited the lowest particle size (PS), polydispersity index (PDI) and the highest zeta potential (ZP), encapsulation efficiency (EE) and mucoadhesive strength was fabricated into spanlastic nano-vesicles ocular insert by solvent casting. In vivo studies showed enhanced bioavailability of travoprost spanlastic nano-vesicles gel and ocular insert compared to the marketed eye drops (travoswix®), as proven by their higher C max and AUC0-∞, in addition to being nonirritant to ocular surfaces. However, spanlastic nano-vesicles ocular insert showed more prolonged effect than spanlastic nano-vesicles gel. According to our study, it can be suggested that travoprost spanlastic nano-vesicles ocular insert is a novel ocular delivery system for glaucoma treatment

In vitro and in vivo evaluation of cyclosporine-graphene oxide laden hydrogel contact lenses

Drug-eluting contact lens can substitute the multiple eye drop therapy. However, loading hydrophobic drug like cyclosporine in the contact lens is very challenging, due to low drug uptake (via soaking method); and alteration in the swelling and optical properties which restricts its clinical application. To address the above issues, graphene oxide (GO, large surface area with oxygen containing functional groups) was incorporated in the contact lenses during fabrication. These GO-laden contact lenses (SM-GO-Cys) as well as blank contact lenses (SM-Cys) were soaked in the solution of cyclosporine. Alternatively, cyclosporine-laden contact lenses (DL-Cys-20) and cyclosporine-GO-laden contact lenses (DL-Cys-20-GO) were fabricated by adding drug and drug-GO (at various level of GO) during fabrication, respectively. Contact angle and swelling data showed increase in water holding capacity of GO laden contact lenses. Optical property was significantly improved due to molecular dispersion of drug on the surface of GO sheets. The drug uptake and in vitro release profile was improved with GO-laden contact lenses by soaking method (SM-GO-Cys-400n) due to hydrophobic interactions between GO and drug. Adding cyclosporine-GO (DL-Cys-20-GO-800n) during fabrication significantly improved drug release kinetics with higher drug leaching (during extraction and sterilization) due to increased swelling, improved dissolution and molecular dispersion of drug on GO sheets. Ocular irritation and histopathological studies demonstrated the safety of GO-contact lens. The in vivo drug release studies in the rabbit eye showed significant improvement in mean residence time (MRT) and area under the curve (AUC) using DL-Cys-20-GO-800n contact lens compared to eye drop solution with reduction in protein adherence value. The study demonstrated that the incorporation of GO into the contact lens can control the release of cyclosporine as well as improved the lens swelling and transmittance properties.

RETRACTED: Extended ocular delivery of latanoprost from niosome-laden contact lenses: In vitro characterization and in vivo studies

Glaucoma affecting the socioeconomic status of patients is currently managed by eye drop solutions, which are highly inefficient due to low ocular bioavailability. Contact lenses can be used to extend the release of ophthalmic drugs. However, the conventional soaking method showed low drug uptake and high burst release, and the optophysical properties of the contact lens were altered for clinical application. In this study, novel latanoprost-loaded niosomes were developed to increase the latanoprost loading capacity of contact lenses while also sustaining ocular drug delivery. Latanoprost-loaded niosomes were prepared by the thin film hydration technique with three levels of cholesterol. The niosome-laden lenses (SM-LT-N-CL) led to improved swelling, transmittance, oxygen permeability and lysozyme adherence of the lens compared to the conventional soaked lens (LT-SM-CL). The in vitro drug release data of LT-SM-CL (up to 24 h) showed high burst release, while SM-LT-N-CL batches showed prolonged release up to 48–96 h. In a rabbit model study, the SM-LT-N-150-CL batch showed a high drug concentration at all time points compared to the LT-SM-CL and eye drop solution. The SM-LT-N-150-CL lens was found to be safe based on histopathological studies. The study demonstrated the successful delivery of latanoprost from a niosome-laden contact lens for an extended period of time without altering the optophysical properties of the contact lens.

RETRACTED ARTICLE: Ofloxacin-Loaded Niosome-Laden Contact Lens: Improved Properties of Biomaterial for Ocular Drug Delivery

Currently, bacterial conjunctivitis is managed by multiple antibiotic eye-drop solution, which is highly inefficient due to low ocular bioavailability and frequent dosing. Therapeutic soft contact lenses can be used to sustain the release of ocular drugs. However, the conventional soaking method (economic and widely used) showed low drug uptake and high burst release, and the optophysical properties of the contact lens were altered for clinical application. In this paper, novel ofloxacin-loaded niosomes were developed to increase the drug loading capacity of contact lenses while also sustaining ocular drug delivery. Ofloxacin-loaded niosomes were prepared by the thin film hydration technique with three levels of cholesterol. The niosome-laden contact lenses (OFL-Nio-L) led to improved optophysical properties (swelling, transmittance, oxygen permeability) and lysozyme adherence compared to the conventional soaked contact lens (CV-OFL-L). The in vitro drug release data of CV-OFL-L showed high burst release, while OFL-Nio-L lenses showed sustained release up to 48-96h. In a rabbit tear fluid model, the OFL-Nio-100-L lens showed a high drug concentration at all-time points compared to the CV-OFL-L and eye-drop solution. The efficacy study in the rabbit model showed improved healing effect with OFL-Nio-100-L lens compared to frequent eye-drop therapy. In conclusion, the paper demonstrated the successful application of niosomes to deliver ofloxacin using contact lens without affecting the critical lens properties to substitute eye-drop therapy.

The effect of tamarind seed polysaccharidecontaining eye drop in dry eye syndrome: Results of an interventional, comparative, clinical study

Background: The mainstay of dry eye treatment is artificial tear solutions. Contralateral eye comparison of 2 types of artificial tears (Xiloial versus Tearlose) in managing dry eye disease was sought in this study.&#x0D; Methods: This study was a prospective, interventional, contralateral eye comparison of 2 types of artificial tears used for managing dry eye disease. The study participants were categorized into mild (13–22 points), moderate (23–32 points), or severe (33–100 points) ocular surface disease according to the baseline ocular surface disease index (OSDI) questionnaire score. Schirmer I and tear film break-up time (TBUT) tests, as well as detailed slit-lamp examinations, were performed at baseline and at the end of the study. All participants received Xiloial monodose eye drops for the right eye and Tearlose eye drops for the left eye, administered as a single drop 4 times per day. Furthermore, they were instructed to perform lid hygiene every 12 hours per day for both eyes.&#x0D; Results: Thirty-five patients (70 eyes) with a mean ± standard (SD) age of 50.2 ± 13.4 years were included, and 14 (40%) were men. The mean ± SD of the OSDI score was 44.24 ± 22.59 at baseline. Of the 35 patients, 10 (28.6%), 5 (14.3%), and 20 (57.1%) had mild, moderate, and severe ocular surface disease, respectively, according to the baseline OSDI score. Compared to baseline, the mean values of both TBUT and Schirmer I tests improved significantly in both groups (both P &lt; 0.001). In comparing the final mean values between the 2 groups, this improvement was comparable for the Schirmer I test (P = 0.179), but TBUT in Tearlose-instilled eyes improved significantly more than in the fellow eyes (P &lt; 0.001).&#x0D; Conclusions: Both Xiloial and Tearlose eye drops improved tear stability and tear production after a 2 week treatment period in eyes with dry eye disease. This improvement was comparable for tear production, but Tearlose-instilled eyes showed significantly greater improvement in tear stability. Further studies with longer follow-up and larger sample sizes could provide more reliable results as a basis for the clinical use of this TSP-containing lubricant eye drop solution in dry eye disease.

Sustained latanoprost release from PEGylated solid lipid nanoparticle-laden soft contact lens to treat glaucoma

Contact lens have been proposed as a mean of ocular drug delivery, but the conventional soaking method to load hydrophobic drugs, such as latanoprost shows low drug loading and high burst release with alteration in the critical lens properties. In this paper, a novel latanoprost-loaded PEGylated solid lipid nanoparticles (LP-pSLNs) were developed to increase the latanoprost loading capacity of contact lenses (LP-pSLN-L), while also sustaining ocular drug delivery. The pSLNs were spherical in shape with an average size of 105‒132 nm (nanometer) and a zeta potential ranging from ‒29.1 to ‒26.7 mV (millivolt). The LP-pSLNs led to improved swelling, transmittance, and protein adherence of the lens compared to the non-pegylated SLNs congeners (LP-SLN-L) and conventional soaked lens (LP-SM-L). The LP-SM-L lens showed low drug loading, high burst release, and a short release duration of 24 h. The LP-SLN-L and LP-pSLN-L lenses showed high drug uptake and sustained drug release up to 120 h and 96 h, respectively. The pegylation reduced the size of nanoparticles and improved the drug loading capacity, while the release rate was high in the initial hours. The LP-pSLN-L lens was found to be safe based in histopathological studies. In animal studies, the LP-pSLN-10-L batch showed high drug concentration at all-time points up to 96 h compared to the LP-SM-L and eye drop solution. In conclusion, pSLNs improved the latanoprost loading in the contact lens and showed sustained drug release, and thus can be used as a substitute to eye drop therapy.

Difluprednate-Hydroxypropyl-β-Cyclodextrin-Based Ophthalmic Solution for Improved Delivery in a Porcine Eye Model.

Purpose: Difluprednate (DFP) is an approved corticosteroid, available as an ophthalmic emulsion (Durezol®), used to treat pain and inflammation of the eye following ocular surgeries. This study utilized hydroxypropyl-β-cyclodextrin (HPBCD)-based DFP ophthalmic solution for improved ocular delivery. Methods: The DFP-HPBCD complex formation was studied in the liquid and solid states. Phase solubility, molecular docking studies, differential scanning calorimetry, and Fourier transform infrared spectroscopy suggested inclusion complexation of DFP and HPBCD. Results: DFP-HPBCD-based eye drops (solution) provided 16 and 26 times higher transcorneal permeation when compared to the suspension (no HPBCD, control) and Durezol, respectively (P < 0.001). In addition, ocular drug distribution studies conducted in continuously perfused whole porcine eyes showed DFP permeated into all of the ocular tissues in significantly higher amounts than Durezol. Conclusions: The solution-based eye drops in this study is iso-osmotic, safe, and more permeable in porcine eyes compared to Durezol.

RETRACTED: Travoprost-loaded PEGylated solid lipid nanoparticle-laden silicone contact lens for managing glaucoma

Conventional methods of soaking contact lenses (CLs) using drug-packaging solutions to load hydrophobic drugs, such as travoprost (TP), result in low drug loading and high burst release, along with changes in the critical properties of the lens. In this study, as a substitute for eye drop therapy, travoprost-loaded PEGylated solid lipid nanoparticles (TP-pSLNs) were used to improve the drug loading capacity of contact lenses (TP-pSLN-CLs), while also sustaining ocular drug delivery to prolong the anti-glaucoma effect. The pSLNs were spherical in shape with an average hydrodynamic diameter of 221–257 nm and a zeta potential ranging from −27.3 to −20.4 mV. The pSLNs led to improved swelling, optical transmittance, and protein adherence of the CLs compared to the non-PEGylated SLN congeners (TP-SLNs-CL) and conventional soaked lens (SM-TP-CL). The SM-TP-CL lens showed low travoprost uptake, high burst release, and a short release duration of up to 48 h. The TP-SLN-CL and TP-pSLN-CL lenses showed high drug uptake and sustained release for up to 144 h and 120 h, respectively. Although PEGylation increased the drug loading capacity, the release rate was high in the initial hours. Based on histopathological analysis, TP-pSLN-CLs were found to be safe and did not induce ocular irritation. In the rabbit tear fluid model, the TP-pSLN-20%CL batch showed high drug concentration at all time points up to 120 h compared to the SM-TP-CL (48 h) and eye drop solution (2 h). In conclusion, by using the soaking method, pSLNs improved the travoprost loading/uptake in the contact lens and improved the in vitro and in vivo results for better clinical outcomes in glaucoma treatment.

Controlled bimatoprost release from graphene oxide laden contact lenses: In vitro and in vivo studies

Ocular drug delivery using contact lenses may be able to substitute for eye drop therapy. However, issues with hydrophobic drugs (like bimatoprost that is used to treat glaucoma) such as low drug uptake using a simple soaking method into preformed contact lenses and alteration in the swelling and transmittance of lenses restricts the application for drug delivery. This research uses graphene oxide (GO) to control the release of bimatoprost from contact lenses along with improvements in the drug uptake, and lens swelling and transmittance. GO was loaded into silicone hydrogel contact lenses by adding the GO at the same time as lenses were polymerized. These lenses were soaked in bimatoprost. Alternatively contact lenses, either with or without GO, were produced by adding bimatoprost during lens polymerization. GO improved contact lens swelling due to its water binding capacity and lens transmittance due to the molecular dispersion of bimatoprost on the surface of the GO which prevented the local precipitation of the drug. The bimatoprost uptake was not improved in the presence of GO. However, its in vitro release profile was improved. Adding bimatoprost and GO at the same time as lenses were polymerized (DL-GO-BMT) significantly decreased the loss of drug during extraction and sterilization in comparison to contact lenses (DL-BMT) without GO. As the amount of GO was increased, the DL-GO-BMT lenses showed a significant decrease in the burst and cumulative release of bimatoprost. Ocular irritation and histopathology reports demonstrated the safety of GO contact lens. The in vivo pharmacokinetic studies in the rabbit tear fluid showed significant improvement in mean residence time (MRT) and area under the curve (AUC) with DL-GO-0.2 μg-BMT-100 contact lens in comparison to eye drop solution. The study demonstrated that the addition of GO to contact lenses can control the release of bimatoprost as well as improved the lens swelling and transmittance. However, further optimization is needed to modulate the release of drug within the therapeutic level to manage glaucoma.

RETRACTED: Controlled brimonidine release from nanostructured lipid carriers-laden silicone contact lens to treat glaucoma

A novel brimonidine-loaded nanostructured lipid carriers (Br-NLCs)-laden silicone contact lenses were designed for control ocular delivery of brimonidine for effective treatment of glaucoma. The Br-NLCs were found to be spherical in shape with an average size of 100–140 nm and a zeta potential of −31.1–33.7 mV. Compared to conventional soaked contact lenses (Br-SM), Br-NLCs-laden contact lenses improved critical lens properties such as swelling, optical transmittance, and protein adherence. Furthermore, Br-SM contact lens showed low brimonidine uptake, high burst release, and short release duration up to 24 h compared to Br-NLCs-laden contact lens that showed high brimonidine uptake, and the cumulative release was sustained up to 144 h. The ability to sustain the release of brimonidine improved proportionally with an increase in the amount of liquid lipid (oleic acid) in the NLCs. The Br-NLCs-laden contact lens was found to be safe in ocular irritation and histopathological studies. In the rabbit tear fluid model, Br-NLC-30%-OA-CL batch showed high brimonidine concentration at all-time points up to 144 h. Further, pharmacodynamic study showed sustained reduction in IOP by Br-NLC-30%-OA-CL batch for 144 h compared to 72 h and 6 h with Br-SM lens and eye drop solution, respectively. In conclusion, Br-NLCs enhanced brimonidine uptake in the contact lens from the soaking solution and showed control brimonidine release to manage glaucoma with better clinical outcomes to substitute eye drop therapy.

Sustained Delivery of Timolol Using Nanostructured Lipid Carriers-Laden Soft Contact Lenses.

The contact lens prepared by the conventional soaking method using timolol-soaking solution showed poor drug uptake and high burst release with altered critical lens properties. In this study, timolol-loaded nanostructured lipid carriers (NLCs) were prepared and evaluated for enhanced timolol uptake and sustained release for the effective management of glaucoma. The characterization studies indicated that timolol-loaded NLCs were spherical in shape with an average size of 130-138 nm and a zeta potential of -46.6 to 51.3 mV. Critical lens properties such as swelling, optical transmittance, and protein adherence were improved with NLC-laden lenses compared to the conventional soaked lenses (SM-TB). Moreover, SM-TB lens showed low timolol uptake, high burst release, and short release duration up to 24 h compared to timolol-NLC-laden lens that showed high timolol uptake, and the cumulative release was sustained up to 96 h. The ability to sustain timolol release improved proportionally with an increase in the amount of Capmul MCMC8 (liquid lipid) in NLCs. In addition, NLC-laden lens was found to be safe according to the results of ocular irritation and histopathological studies. In the rabbit tear fluid model, NLC-30%-Cap-CL batch showed high timolol concentration at all time points up to 60 h. Further, pharmacodynamic study showed sustained reduction in IOP by NLC-30%-Cap-CL batch for 96 h compared to 48 h and 6 h with SM-TB lens and eye drop solution, respectively. In conclusion, NLCs enhanced timolol uptake in the contact lens from the soaking solution using soaking method with improved in vitro and in vivo results for better clinical outcomes in the patients with glaucoma.

Nepafenac loaded ophthalmic nanocarriers for treatment of uveitis: A review

Visual impairment (VI), a worldwide worry that is probably going to raise with delayed futures, has gained increasing attention in the domain of eye care. Now a days, new cases of visual impairment occur in older individuals, some children are born with visual impairments resulting from retinopathy of prematurity, a condition associated with premature birth. Other children experience vision loss because of congenital glaucoma or congenital cataracts, Uveitis and some experience vision loss of unknown etiology. Uveitis is an intraocular inflammation involving primarily the uveal tract. Vision is one of our most cherished senses. There are nearly 45 million people worldwide who are blind and a further 135 million people are visually disabled. Uveitis causes 0.6% - 11% of blindness in various studies. The ophthalmic preparations are available as buffered, sterile and isotonic solution. For the ocular delivery of drugs, several types of dosage forms are prepared and marketed. As drops are easier to administer so the most prescribed dosage form is the eye drop solution. Nepafenac is unique among ophthalmic NSAIDs in that it is a prodrug deaminated to amfenac, a highly effective non-selective cyclooxygenase inhibitor. The compiled data presented in this review will act as a good information resource and reference point for further research in the field of ocular drug delivery aiming non-invasive sustained release of drugs in the anterior and posterior segments of the eye.

In vitro and in vivo evaluation of ketotifen-gold nanoparticles laden contact lens for controlled drug delivery to manage conjunctivitis

To overcome the limitations of eye drop solutions, contact lenses are widely used for controlled ophthalmic drug delivery. However, drug-laden contact lenses prepared by traditional soaking technique show poor drug uptake, high burst release, and altered critical lens properties. In the current paper, the effect of gold nanoparticles (GNPs) on ketotifen uptake from the drug-soaking solution and its release kinetics from the lens was investigated. In one method, GNPs solutions of varying strength were loaded into the ketotifen-soaking solution (mM-GNPs-SS batches), and in another method, the GNPs were incorporated in the contact lens during fabrication (mM-GNPs-L batches). The GNPs were spherical, with an average diameter of 17.2 nm and a zeta potential of −21.2 mV. The contact lens's swelling, oxygen permeability, and optical transmittance were improved when compared to lenses prepared by traditional soaking method (K-SM-L). The mM-GNPs-L lenses showed substantial improvement in drug uptake from the ketotifen-soaking solution compared to the K-SM-L and mM-GNPs-SS lenses. The in vitro experiments showed low burst and control ketotifen release up to 96 h, compared to 48 h with the K-SM-L lens. The ability to sustain ketotifen release profile improved proportionally with an increase in the amount of GNPs in the lens. The protein adherence was reduced with the presence of GNPs in the contact lens. The GNPs-laden lenses were found to be safe in ocular irritation and histopathology reports (rabbit model). Further, they showed higher ketotifen retention in the rabbit tear fluid compared to the K-SM-L lens and eye drop solution. Thus, the presence of GNPs in contact lenses increased ketotifen uptake from the soaking solution, reduced burst release, and improved the in vitro and in vivo release kinetics without affecting the critical lens properties for therapeutic application.

A long-term retaining molecular coating for corneal regeneration

Corneal injuries will cause corneal surface diseases that may lead to blindness in millions of people worldwide. There is a tremendous need for biomaterials that can promote corneal regeneration with practical feasibility. Here we demonstrate a strategy of a protein coating for corneal injury regeneration. We synthesize an o-nitrosobenzaldehyde group (NB)-modified gelatin (GelNB), which could adhere directly to the corneal surface with covalent bonding to form a thin molecular coating. The molecular coating could avoid rapid clearance and provide a favorable environment for cell migration, thereby effectively accelerating corneal repair and regeneration. The histological structure of the regenerated cornea is more similar to the native cornea. This molecular coating can be used conveniently as an eye drop solution, which makes it a promising strategy for corneal regeneration.

Effect of Lactic Acid Content into on during Miconazole Eye Drops to be Used for Infection Preventive

Purpose: The aims of this study were to prepare a 0.1% Miconazole (MCZ) eye-drop solution and to evaluate the stability and physical properties of the preparation.

Novel Application of Hot Melt Extrusion Technology for Preparation and Evaluation of Valacyclovir Hydrochloride Ocular Inserts.

The objective of this study was to investigate the processability of hot-melt extrusion (HME) to formulate ocular inserts of valacyclovir hydrochloride and evaluate the in vivo bioavailability of the formulation. To optimize the formulation of this drug, different physical mixtures of the polymers and plasticizer were prepared. The physical mixture was extruded through a co-rotating twin-screw extruder, and the obtained ocular inserts were cut with dimensions of 4mm × 2mm × 1mm to enhance the formulation instillation in the eye. Ocular inserts were evaluated for drug content, weight variation, uniformity of thickness, in vitro drug release, and in vivo drug bioavailability. The ocular inserts were thermally characterized using differential scanning calorimetry (DSC). The attributes observed for the ocular inserts were within the target specifications. The ocular inserts of valacyclovir hydrochloride were successfully prepared using the HME. They provided sustained drug release along with enhanced drug permeation when compared with the eyedrop solution and dissolve completely in 8h. Additionally, the obtained results demonstrated that the formulation of ocular inserts of valacyclovir hydrochloride using HME was reproducible, robust, and effective method.

An Exploratory Study of a New Vancomycin Eye Drops Formulation for Extemporaneous Compounding.

Compounded eye drop solutions of vancomycin hydrochloride have important clinical applications, such as postoperative antimicrobial prophylaxis and bacterial keratitis. There exists a plethora of data to support the use of various liquid vehicles to compound vancomycin hydrochloride eye drops. However, there are a number of limitations for implementation, especially the frequent shortage or discontinuation of the vehicle products. This study was designed to investigate the use of an OTC eye wash product as the evergreen vehicle and to evaluate the physical and chemical stability of the new formulation. The Advance Eye Relief® eye wash and vancomycin hydrochloride for injection vials were used to prepare 10 and 50 mg/mL vancomycin eye drop solutions. The solutions were packaged in Steri-Droppers® bottles and stored in a freezer for 14 days followed by 28 days in refrigeration. The 14-day period of freezing was included to allow time for sterility testing. At pre-determined stability time points, samples were taken for visual inspection, pH and osmolality measurement, and analysis by a stability-indicating high performance liquid chromatography (HPLC) method. Freshly prepared vancomycin eye drops were clear, colorless, and free of particulates. The pH readings were 7.03 and 6.28 for the 10 and 50 mg/mL solutions, respectively. The osmolality of both solutions were within the range of 300-330 mOsmol/kg and considered isotonic. Initial drug concentrations of all samples were confirmed by HPLC to be within 100%-103% of the label claims. Throughout the stability study period, there were no significant changes in the appearance, pH, or osmolality of any samples. The HPLC results also confirmed that the drug concentrations in all stability samples were within 98%-101% of the initial time zero values and no significant degradation product peaks were observed. A new compounded vancomycin eye drop formulation was developed to mitigate vehicle sourcing issues. This eye drop formulation was easy to prepare, exhibited satisfactory properties for ophthalmic applications, and remained stable chemically and physically when stored for 14 days in freezer followed by 28 days in refrigerator.

The in vitro efficacy of eye drops containing a bacteriophage solution specific for Staphylococcus spp. isolated from dogs with bacterial conjunctivitis

BackgroundThe purpose of the study was to evaluate the in vitro antibacterial effect of experimental eye drops with bacteriophages in elimination of Staphylococcus spp. isolated from dogs with bacterial conjunctivitis.. The bacterial material was collected from dogs with independent clinical signs of bacterial conjunctivitis. Staphylococcus spp. were identified by phenotypic and genotypic methods (MALDI-TOF MS mass spectrometry). Antibiotic resistance was determined by the disc-diffusion method. Phage activity (Plaque forming units, PFU) was determined on double-layer agar plates. Phages with lytic titres > 108 PFU were used to prepare eye drops. The stability of the antibacterial titre was evaluated for preparations stored in sealed bottles as well as after opening and reclosing.ResultsThe tests confirmed the occurrence of Staphylococcus spp. strains as etiological agents of bacterial conjunctivitis in dogs. A high percentage of strains were resistant to more than three antibiotics. The experimental phage eye drops used in the study exhibited 100% efficacy in vitro against the tested Staphylococcus isolates. Particularly noteworthy is the long duration of activity and constant antibacterial lytic titre of ≥108 PFU/mL of two eye drop solutions, nos. 7 and 12, after the bottle had been opened (21 days) and after hermetically sealed packaging (28 days) at 4–8 °C.ConclusionsThe results represent the first stage of research and require continuation in vivo. If positive effects are obtained in animals, the results can be used in applied research in humans and animals.