Oculohypotensive effects of various acetozolamide nanopreparations for topical treatment of animal model-induced glaucoma and their impact on optic nerve (original) (raw)
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Formulation and evaluation of acetazolamide loaded in–situ gel for the treatment of glaucoma
Journal of research in pharmacy, 2023
The present research work was proposed to develop a pH triggered in-situ gel formulation for the ocular delivery of acetazolamide to treat glaucoma. Carbopol-934, Carbopol 940, Hydroxypropyl methylcellulose (HPMC) K4M, and Sodium Alginate were chosen for the development of in-situ gel. Formulation with Carbopol 940 and sodium alginate was optimized by assessing the gelling capacity. The prepared in-situ gel formulations were thoroughly characterized for gelling time, gelation temperature, Fourier-transform infrared (FTIR) spectroscopy studies, rheological study, sterility testing, corneal drug permeation, ocular irritation test, and accelerated stability study. Ex-vivo corneal permeation study was performed using goat cornea. The result of transcorneal permeation of acetazolamide followed the Fickian diffusion process. The optimized formulations showed satisfactory gelling time (4.17-5.17 sec) and dissolution time (120 min). FTIR study confirms the compatibility between the polymers and acetazolamide. The sterility study showed a satisfactory result. After 72 h observation in the in-vivo rabbit eye irritation study, the eyes appeared normal. There were no significant changes in pH and drug content in the accelerated stability studies of the formulations.
Novel Polymeric Nanoparticles Intended for Ophthalmic Administration of Acetazolamide
Journal of pharmaceutical sciences, 2016
Glaucoma is characterized by increased intraocular pressure (IOP) that results in blindness if it remains untreated. Acetazolamide (AZM) is a carbonic anhydrase inhibitor, mainly used to reduce IOP in the treatment of glaucoma. However, the potential of topical treatment is limited, due to its low permeability across the ocular epithelium. An alternative to overcome this limitation is the incorporation of AZM in nanoparticulate systems, such as polymeric nanocapsules (NCs). In this way, the aim of this work was to prepare and characterize NC formulations containing AZM, using ethylcellulose (EC) and Eudragit(®) RS100 (EUD) as encapsulating polymers. The formulations showed high encapsulation efficiency. Particle size measurements showed that NCs are in the nanometric range. Comparing both groups of formulations, the NCEC proved to be smaller than those prepared with EUD. The formulations prepared with EC showed negative zeta potentials, while NCs of EUD were positively charged. For ...
Pharmaceutics, 2021
The purpose of this study was to design, for the first time, a co-loaded liposomal formulation (CLL) for treatment of glaucoma including timolol maleate (TM) in the lipid bilayer and acetazolamide (Acz)-(2-hydroxy)propyl β-cyclodextrin (HPβCD) complexes (AczHP) solubilized in the aqueous core of liposomes. Formulations with TM (TM-L) and AczHP (AczHP-L), separately, were also prepared and characterized. A preliminary study comprising the Acz/HPβCD complexes and their interaction with cholesterol (a component of the lipid bilayer) was realized. Then, a screening study on formulation factors affecting the quality of the product was carried out following the design of the experiment methodology. In addition, in vitro release and permeation studies and in vivo lowering intraocular pressure (IOP) studies were performed. The results of the inclusion complexation behavior, characterization, and binding ability of Acz with HPβCD showed that HPβCD could enhance the water solubility of Acz de...
Pharmaceutics, 2021
Acetazolamide (ACZ) is a diuretic used in glaucoma treatment; it has many side effects. Carvedilol (CAR) is a non-cardioselective beta-blocker used in the treatment of elevated intraocular pressure; it is subjected to the first-pass metabolism and causes fluids accumulation leading to edema. This study focuses on overcoming previous side effects by using a topical formula of a combination of the two previous drugs. Sixty formulations of niosomes containing Span 20, Span 60, Tween 20, and Tween 60 with two different ratios were prepared and characterized. Formulation with the lowest particle size (416.30 ± 0.23), the highest zeta potential (72.04 ± 0.43 mv), and the highest apparent coefficient of corneal permeability (0.02 ± 0.29 cm/h) were selected. The selected formula was incorporated into the gel using factorial design 23. Niosomes (acetazolamide/carvedilol) consisting of Span 60 and cholesterol in the molar ratio (7:6), HMPC, and carbopol with two different ratios were used. Th...
Colloids and Surfaces B: Biointerfaces, 2014
Poor drug penetration and rapid clearance after topical instillation of a drug formulation into the eyes are the major causes for the lower ocular bioavailability from conventional eye drops. Along with this, poor encapsulation efficiency of hydrophilic drug in polymeric nanoparticles remains a major formulation challenge. Taking this perspective into consideration, Dorzolamide (DZ)-loaded PLGA nanoparticles were developed employing two different emulsifiers (PVA and vitamin E TPGS) and the effects of various formulation and process variables on particle size and encapsulation efficiency were assessed. Nanoparticles emulsified with vitamin E TPGS (DZ-T-NPs) were found to possess enhanced drug encapsulation (59.8±6.1%) as compared to those developed with PVA as emulsifier (DZ-P-NPs). Transcorneal permeation study revealed a significant enhancement in permeation (1.8-2.5 fold) as compared to solution. In addition, ex vivo biodistribution study showed a higher concentration of drug in the aqueous humor (1.5-2.3 fold). Histological and IR-camera studies proved the non-irritant potential of the formulations. Pharmacoscintigraphic studies revealed the reduced corneal clearance, as well as nasolachrymal drainage in comparison to drug solution. Furthermore, efficacy study revealed that DZ-P-NPs and DZ-T-NPs significantly reduced the intraocular pressure by 22.81% and 29.12%, respectively, after a single topical instillation into the eye.
International Research Journal of Pharmacy
The purpose of the study was to formulate topically effective ophthalmic acetazolamide vesicular formulations. Ethanolic and ethereal injection methods were used for the preparation of bi-lamellar and multi-lamellar acetazolamide vesicles consisting of span-60, PEG-400 and PG (co-solvents and penetration enhancers) with or without tween-80 (an edge activator) and non-ionic surfactant. Reverse phase evaporation (REV) method was used to prepare niosomes (control) and 1% w/v acetazolamide suspension for comparison purpose to evaluate ex-vivo corneal permeability performance. The prepared vesicles were evaluated for their abundance, size, shape, lamellarity and number of vesicles/mm 3 by optical microscopy, entrapment efficiency, drug content, zeta potential, pH, DSC studies, ex-vivo corneal permeability studies, sterilization studies, in-vivo studies, stability studies and safety studies. Bi-lamellar and multi-lamellar vesicles entrapped greater amounts of drug than uni-lamellar REVs niosomes. Physical stability study indicated that approximately 93% and 94% of acetazolamide was retained in selected vesicular formulations up to a period of 4 months at 4°C. The intraocular pressure (IOP) lowering activity of selected acetazolamide vesicular formulations was determined and compared with Dorzox ® , a marketed formulation. Acetazolamide vesicles revealed more prolonged effect than marketed formulation. The selected vesicular formulations F1 and F2 exhibited greater lowering in IOP and a more prolonged effect than the other formulations prepared by ethanolic injection and ethereal injection methods without co-solvents. The selected vesicular formulation F1 composed of PEG 400PG (1:7) ratio and formulation F2 composed of PEG-400 without PG showed the maximal response, which reached a value of-3.3±0.4 mmHg after 1 hour of topical administration.
Development and Characterization of Acetazolamide Nanoemulsion for Effective Ocular Delivery
International Journal of Life Science and Pharma Research, 2021
Nanoemulsion has the potential of releasing the drug continuously, and they may easily permeate via the intense layers of the eye structure due to nano-size droplets, which makes nanoemulsion an effective drug delivery system for ocular delivery. The objective of our work was to prepare a nanoemulsion of acetazolamide for glaucoma treatment with enhanced efficacy as well as for continuous effect. Based on different compositions of oil (Olive Oil), surfactants (Tween-20), and co- surfactants (Transcutol P), forty-five test mixtures were made, water titration technique was employed for preparing the pseudo-ternary-phase diagrams. On the basis of these phase diagrams, twenty-five acetazolamide loaded nanoemulsion were formulated and examined for their nanosized droplets, PDI, zeta potential, viscosity, pH, transmittance and in-vitro drug release. The formulated nanoemulsion showed all the properties within the desired range i.e., droplet size (15.6 to...
Nanotechnology Applications to Treat Glaucoma
Glaucoma is a disease caused by the inability of the intraocular pressure to stabilize and the intraocular fluid to be released in sufficient quantities. High pressure causes damage to the optic nerve, which causes the patient's visual field to gradually narrow. Four classes can be separated. Today's traditional treatment methods are not enough. These are drugs and surgical interventions. Drug therapy is not efficient, but surgical interventions also involve risks. Progressive nanotechnology allows for more effective drug applications and surgical methods that offer less risky and precise solutions. What is glaucoma in this study, why does it occur, what are the current treatment methods, what are the modern treatment methods, and what advantages did nanotechnology have in glaucoma treatment?
Advanced trends in treatment of glaucoma
Glaucoma is a slow escalating disease which causes the degradation of the retinal ganglionic cells (RGCs). It eventually results in irrevocable blindness if it is not diagnosed properly in time. The various important factors which are present in glaucoma are-increased intraocular pressure, increased glutamate levels, oxidative damage and changes in nitric oxide metabolism. The goal is to reduce the intraocular pressure which can be done by medications, laser procedures, surgical procedures and intraocular devices. The drugs used for the treatment of glaucoma are prostaglandin analogs, alpha-agonists, carbonic anhydrase inhibitors and cholinergic agonists. In ophthalmic formulations, emulsions, suspensions and soluble ophthalmic drug inserts (SODI) use of viscoelastic agents have been used in order to enhance the ocular drug delivery in patients as well as to provide a sustained release effect and better therapeutic action. It was observed that some patients are immune to medications and later have to resolve to laser procedures and surgical procedures. The future anti-glaucoma drug or technique should reduce intraocular pressure. It must also be neuroprotective and vasoprotective in nature and restore visual acuity.
Nanotechnology for Medical and Surgical Glaucoma Therapy—A Review
Advances in Therapy, 2019
Glaucoma is the second leading cause of blindness worldwide. Even though significant advances have been made in its management, currently available antiglaucoma therapies suffer from considerable drawbacks. Typically, the success and efficacy of glaucoma medications are undermined by their limited bioavailability to target tissues and the inadequate adherence demonstrated by patients with glaucoma. The latter is due to a gradual decrease in tolerability of lifelong topical therapies and the significant burden to patients of prescribed stepwise antiglaucoma regimens with frequent dosing which impact quality of life. On the other hand, glaucoma surgery is restricted by the inability of antifibrotic agents to efficiently control the wound healing process without causing severe collateral damage and long-term complications. Evolution of the treatment paradigm for patients with glaucoma will ideally include prevention of retinal ganglion cell degeneration by the successful delivery of neurotrophic factors, anti-inflammatory drugs, and gene therapies. Nanotechnology-based treatments may surpass the limitations of currently available glaucoma therapies through optimized targeted drug delivery, increased bioavailability, and controlled release. This review addresses the recent advances in glaucoma treatment strategies employing nanotechnology, including medical and surgical management, neuroregeneration, and neuroprotection.