Cationic liposomes as promising vehicles forTimolol/Brimonidine combination ocular delivery in glaucoma: Formulation development and in vitro/in vivo evaluation (original) (raw)
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International Journal of Pharmaceutics, 2018
Glaucoma treatment with ocular medications requires overcoming the corneal barrier to drug penetration. Liposomes have a great corneal penetration ability and affinity while suffering from poor stability and low entrapment of hydrophilic drugs accompanied by rapid drug release. This work aims to develop a new, effective and stable glaucoma medication with sustained drug release properties; Timolol maleate gelatinized core liposomes. A full factorial design was utilized to study the effects of three formulation variables on drug loading and vesicle particle size. Vesicles were prepared by the thin-film hydration method, and characterized for in-vitro drug release and stability. Intra-ocular pressure (IOP) reduction was evaluated in-vivo on glaucomatous rabbit's eyes. The safety profile was assessed using histolopthological examinations. Gelatin significantly increased the drug entrapment percentage reaching 50% with a particle size of 38.81 µm. Sustained drug release was recorded compared to a marketed product and to a conventional liposomal formulation. The prepared vesicles caused the highest reduction in IOP accompanied by safe histological findings. This work provided a new, safe and effective ocular glucauma medication; Timolol maleate gelatinized core liposomes, solving the main problems of ocular liposomal formulations of hydrophilic drugs.
Preparation and evaluation of liposomes of brimonidine tartrate as an ocular drug delivery system
Int. J. Res. Pharm. Sci …, 2010
Nioosomes of brimonidine tartrate were prepared by film hydration method. The prepared vesicles were evaluated for photomicroscopic characteristics, entrapment efficiency, in vitro, ex-in vitro drug release, in vivo intra ocular pressure lowering activity. Methods employed for the preparation of vesicles were found to be simple and reproducible, produced vesicles of acceptable shape and size with unimodal frequency distribution pattern. The in vitro, ex-in vitro drug release studies showed that there was a slow and prolonged release of drug which followed zero order kinetics. The intra ocular pressure lowering activity of prepared formulations were determined and compared with pure drug solution. It was found that intra ocular pressure lowering action was sustained for longer period of time. Stability study data revealed that the formulations were found to be stable when stored at refrigerator temperature (2 °C to 8 °C) and at 25 °C with no change in shape and drug content. Results of the study indicated that it is possible to develop a safe and physiological effective topical niosomal formulation which is patient compliance.
Preparation and evaluation of liposomes of brimonodine tartrate as an ocular drug delivery system
International Journal of Research in Pharmaceutical Sciences
Nioosomes of brimonidine tartrate were prepared by film hydration method. The prepared vesicles were evaluated for photomicroscopic characteristics, entrapment efficiency, in vitro, ex-in vitro drug release, in vivo intra ocular pressure lowering activity. Methods employed for the preparation of vesicles were found to be simple and reproducible, produced vesicles of acceptable shape and size with unimodal frequency distribution pattern. The in vitro, ex-in vitro drug release studies showed that there was a slow and prolonged release of drug which followed zero order kinetics. The intra ocular pressure lowering activity of prepared formulations were determined and compared with pure drug solution. It was found that intra ocular pressure lowering action was sustained for longer period of time. Stability study data revealed that the formulations were found to be stable when stored at refrigerator temperature (2 °C to 8 °C) and at 25 °C with no change in shape and drug content. Results of the study indicated that it is possible to develop a safe and physiological effective topical niosomal formulation which is patient compliance.
International Research Journal of Pharmacy, 2015
In this study liposomes were developed and evaluated for timolol maleate (TM) and latanoprost (LP) by lipid film hydration technique for the treatment of glaucoma. A 3 2 factorial design was utilized to study the effect of the molar ratio of 1, 2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPCC) (X1) and cholesterol (X2) on vesicle size, drug entrapment efficiency and in-vitro release study. Fourier transform infrared spectroscopy (FT-IR) studies were performed to investigate and predict any physiological interactions between components in the formulation. The liposomal vesicles were found to be uniform in size and shape. The drug entrapment efficiency values for the seven batches showed a variation from a minimum of 56.65 ± 1.39 % to maximum of 70.24 ± 1.14 %. This clearly indicates that the drug entrapment value is strongly dependent on the variables selected. The Zeta potential, average particle size and poly dispersibility index was found to be-17.3 mV, 240 nm and 0.114 respectively. Most of the formulations were found to have a linear release and the formulations were found to provide approximately 72 %-55 % of drug release for TM and LP respectively within a period of 6 h. Kinetic study reveals that release mechanism depends on swelling, diffusion and relaxation. Best formulation (F2) was found to be sterile and stable and free from microorganisms and passes the isotonicity test. Reduction in intra ocular pressure (IOP) was greater in liposomes as compared to the marketed product of alone and combination medication. A latanoprost-timolol maleate fixed combination, has the advantage of a more convenient delivery system as well as providing a simple summing effect of the two constituents.
Due to the drawback of conventional therapy for ocular delivery like poor bioavailability of drugs due to tear production, non productive absorption, transient residence time, impermeability of corneal epithelium. These problems can be minimized by the application of niosomal vesicular system as well as combination of drugs provides the additive effect on reduction of IOP. The aim of the present study was to develop niosomal combination formulation of timolol maleate and brimonidine tartrate for the treatment of glaucoma. Niosomal formulations of brimonidine tartrate and timolol maleate were prepared by film hydration method. Span 60 and cholesterol used as an excipient. White rabbits of both sexes, weighing between 2 to 3 kg were used for the study. The prepared vesicles were evaluated for photomicroscopic characteristics, entrapment efficiency, in vitro, ex-in vitro drug release, in vivo intra ocular pressure lowering activity. Methods employed for the preparation of vesicles were found to be simple and reproducible, produced vesicles of acceptable shape and size with unimodal frequency distribution pattern. The in vitro, ex-in vitro drug release studies showed that there was a slow and prolonged release of drug which followed zero order kinetics. The intra ocular pressure lowering activity of prepared formulations were determined and compared with pure drug solution. It was found that intra ocular pressure lowering action was sustained for longer period of time which provides additive effect with combination. Stability study data revealed that the formulations were found to be stable when stored at refrigerator temperature (2 °C to 8 °C) and at 25 °C with no change in shape and drug content. Results of the study indicated that it is possible to develop a safe and physiological effective topical niosomal formulation which is patient compliance. IOP lowering activity of the combination of timolol maleate and brimonidine tartrate in niosomes was better as compared to alone medication, which shows the additive effect of combination medication.
Augmented in vitro and in vivo Profiles of Brimonidine Tartrate Using Gelatinized-Core Liposomes
International Journal of Nanomedicine
Background: The low entrapment efficiency of the hydrophilic drugs such as brimonidine tartrate (BRT) in liposomes represents a challenge that requires interventions. Gelatinized core liposomes (GCLs) were fabricated to increase the drug entrapment, corneal penetration, and physical stability of the investigated molecule. Research Design and Methods: GCLs encapsulating BRT were prepared and optimized utilizing D-optimal design (DOD). The effect of plasticizer incorporation on the physicochemical characteristics and on the in vivo performance was studied. The optimized formulations were investigated for pH, rheological properties, morphological characteristics, in vitro release profiles, biological performance, safety profile. The effects of storage and gamma sterilization were also investigated. Results: The results revealed the great success of the prepared formulations to achieve high entrapment efficiency reaching 98% after a maturation period of 10 days. The addition of glycerol as plasticizer significantly minimized the particle size and shortened the maturation period to 7 days. The selected formulations were stable for 3 months after gamma sterilization. The formulations showed significant lowering of intra-ocular pressure (IOP) in glaucomatous rabbits with sustainment of the pharmacological effect for 24 hours compared to drug solution. Conclusions: Enhanced in vitro and in vivo profiles of brimonidine tartrate loaded gelatinized-core-liposomes were obtained.
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...
APPLICATIONS OF LIPOSOMES IN OPHTHALMIC DRUG DELIVERY SYSTEM
Drug delivery research to the eye has gathered momentum over the past few years in an attempt to overcome the eyes natural barriers to drugs. Since the eye can be affected by a multitude of diseases such as infections and degeneration, novel modes of targeting disease sites within the eye are required. One way of achieving this is by the incorporation of drugs into liposomes which provide a safe and effective method of drug delivery. Liposomes are microparticulate lipoidal vesicles which are under extensive investigation as drug carriers for improving the delivery of therapeutic agents to different organs including eye. Reformulation of drugs in liposomes has provided an opportunity to enhance the therapeutic indices of various agents mainly through alteration in their biodistribution and their stay at target. This review discusses the potential applications of liposomes in ophthalmic drug delivery with examples of formulations approved for clinical use, and the problems associated with further exploitation of this drug delivery system.
Liposomes as ocular drug delivery platforms : A review
2017
Topically applied drugs need to overcome physiological, anatomical and dynamic barriers in the ocular milieu for effective ocular penetration. There exists an urgency to develop novel approaches for the treatment of ophthalmic complications such as glaucoma, uveitis, retinitis, age related macular degeneration, diabetic retinopathy, retinitis pigmentosa. Efflux protein pumps present in the ocular tissues restrict the ocular absorption. Novel drug delivery strategies and approaches could improve ocular bioavailability of drugs which would be beneficial for the intervention of disorders. At present, the intravitreal route is widely used for posterior ophthalmic delivery. Over the past few years, liposomal systems were being exploited and targeted for posterior ocular delivery due to their unique structural framework to entrap lipophilic/hydrophilic drugs. The present review discusses about the recent advances the niche of liposomal ocular delivery.
Ocular Drug Delivery System:-A review Corresponding Author: XXXXX
Eye diseases are commonly encountered in day to day life, which are cured or prevented through the conventionally used dosage forms like eye drops, ointments. Delivery to the internal parts of the eye still remains troublesome due to the anatomical and protective structure of the eye. To overcome these problems various types of dosage forms such as nanoparticles, liposomes and micro emulsions have been developed. Ocular drug delivery is one of the most challenging tasks faced by Pharmaceutical researchers. Major barriers in ocular medication are the ability to maintain a therapeutic level of the drug at the site of action for a prolonged duration. The anatomy, physiology, and biochemistry of the eye is such that it is impervious to foreign substances, therefore, it is a challenge for the formulator to pass through the protective barriers of the eye without causing any permanent tissue damage. The introduction of new sensitive diagnostic techniques and therapeutic agents necessitates the development of a successful and advanced ocular drug delivery system. Current momentum in the invention of new drug delivery systems hold a promise toward much improved therapies for the treatment of vision, threatening disorders.