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1.
Drug Dev Ind Pharm ; 46(4): 673-681, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32233932

ABSTRACT

The aim was to reveal the characteristic profiles of the marketed levofloxacin eye drops (5 mg/ml) and levofloxacin eye gel (3 mg/g) from the pharmacokinetics and pharmacodynamics views of rabbits' eyes. A mild and a heavy bacterial keratitis models in rabbits were established. Different regimens of levofloxacin eye drops and eye gel, including phosphate buffer solution (the PBS group), the 4-Sol + 1-Gel group (rabbits were treated with 4 doses of levofloxacin eye drops and 1 dose levofloxacin eye gel per day), the 3-Sol + 1-Gel group (3 doses drops and 1 dose gel), the 4-Sol group (4 doses drops), the 4-Gel group (4 doses gel), the 3-Sol group (3 doses drops), and the 3-Gel group (3 doses gel), were applied to evaluate their efficacies. The ocular pharmacokinetics of levofloxacin eye drops and gel were also investigated. The results of mild infection groups showed that all treatment regimens significantly relieved the infection symptoms, and the treatment effect followed this order: 4-Gel > 4-Sol + 1-Gel > 3-Sol + 1-Gel > 4-Sol > 3-Gel > 3-Sol. In the heavy infection groups, all the treatment regimens significantly relieved the infection symptoms, and the treatment effect also followed the order with the mild infection results. All treatment regimens lowered the number of corneal colony forming units (CFU). Levofloxacin eye gel significantly increased intraocular penetration in rabbits' eyes. It can be concluded that the levofloxacin eye gel was more effective in treating bacterial keratitis than the levofloxacin eye drops in rabbit keratitis model with a proper treatment regimen such as 4-Gel.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Keratitis/drug therapy , Levofloxacin/administration & dosage , Ophthalmic Solutions/administration & dosage , Staphylococcal Infections/drug therapy , Administration, Ophthalmic , Animals , Colony Count, Microbial , Disease Models, Animal , Gels , Humans , Keratitis/microbiology , Microbial Sensitivity Tests , Ocular Absorption/drug effects , Rabbits , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects , Staphylococcus aureus/isolation & purification
2.
Article in English | MEDLINE | ID: mdl-28499206

ABSTRACT

This study aims to establish a fast and sensitive LC-MS/MS method for simultaneous determination of seven alkaloids from Rhizoma Corydalis Decumbentis in rabbit aqueous humor. Aqueous humor samples were processed by protein precipitation and then separated on a Thermo Syncronis C18 column (50mm×2.1mm, 5µm) with a mobile phase using acetonitrile-0.05% formic acid (28:72, v/v). Detection of the analytes and the internal standard (coptisine) were performed in positive electrospray ionization with selected reaction monitoring. The method showed good linearity (r>0.9931) for all the seven alkaloids. This fully validated method was applied to the studies of aqueous humor pharmacokinetics of seven alkaloids from Rhizoma Corydalis Decumbentis and the effects of borneol on corneal penetration of these alkaloids into aqueous humor. This is the first work that presents a reliable LC-MS/MS method for simultaneous determination of seven alkaloids in rabbit aqueous humor and its application of ocular pharmacokinetics of seven alkaloids from Rhizoma Corydalis Decumbentis.


Subject(s)
Alkaloids/analysis , Alkaloids/pharmacokinetics , Aqueous Humor/chemistry , Aqueous Humor/metabolism , Corydalis/chemistry , Drugs, Chinese Herbal/pharmacokinetics , Animals , Camphanes/pharmacology , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , Ocular Absorption , Rabbits , Rhizome/chemistry , Sensitivity and Specificity , Tandem Mass Spectrometry/methods
3.
Pak J Pharm Sci ; 28(1): 1-7, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25553687

ABSTRACT

The permeability of most drugs through the eyes is very limited, so finding safe and effective penetration enhancers is of high importance in current ophthalmology research. In this paper, we use a new approach that integrates Chinese and Western medicine to improve the corneal permeability of baicalin, a water- and fat-insoluble target drug, in vitro. Rabbits were divided into three groups. The first group was dosed with borneol (0.05%, 0.1%). menthol (0.1%, 0.2%), or Labrasol (1%, 2%) individually, the second was dosed with a combination of Labrasol with either borneol or menthol, and the third group received a control treatment. Compared with the control treatment, borneol, menthol, or Labrasol alone clearly improved the permeability of baicalin in vitro. Furthermore, the penetrating effects were significantly increased by combining the application of Labrasol with menthol or borneol. Among the various combined penetration enhancers, 0.1% borneol with 2% Labrasol achieved the best apparent permeability, approximately 16.35 times that of the control. Additionally, the calculation of corneal hydration level and the Draize test demonstrated the safety of these penetration enhancers to the rabbit corneas in vivo. This study confirms that the combined use of borneol or menthol, compounds both derived from Chinese herbs, with Labrasol can improve the corneal permeability of water- and fat-insoluble drugs.


Subject(s)
Camphanes/pharmacology , Cornea/drug effects , Drugs, Chinese Herbal/pharmacology , Flavonoids/metabolism , Menthol/pharmacology , Ocular Absorption/drug effects , Animals , Camphanes/toxicity , Chemistry, Pharmaceutical , Cornea/metabolism , Drug Combinations , Drugs, Chinese Herbal/toxicity , Flavonoids/chemistry , Glycerides , Kinetics , Menthol/toxicity , Organic Chemicals/pharmacology , Organic Chemicals/toxicity , Permeability , Rabbits , Solubility
4.
J Pharm Sci ; 104(1): 63-71, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25394188

ABSTRACT

In this paper, an ex vivo model for the study of the transcorneal permeation of drugs, based on porcine tissues, was evaluated. The setup is characterized by ease of realization, absence of O2 and CO2 bubbling and low cost; additionally, the large availability of porcine tissue permits a high throughput. Histological images showed the comparability between porcine and human corneas and confirmed the effectiveness of the isolation procedure. A new de-epithelization procedure based on a thermal approach was also set up to simulate cornea permeability in pathological conditions. The procedure did not affect the integrity of the underlying layers and allowed the characterization of the barrier properties of epithelium and stroma. Six compounds with different physicochemical properties were tested: fluorescein, atenolol, propranolol, diclofenac, ganciclovir and lidocaine. The model highlighted the barrier function played by epithelium toward the diffusion of hydrophilic compounds and the permselectivity with regard to more lipophilic molecules. In particular, positively charged compounds showed a significantly higher transcorneal permeability than negatively charged compounds. The comparability of results with literature data supports the goodness and the robustness of the model, especially taking into account the behavior of fluorescein, which is generally considered a marker of tissue integrity.


Subject(s)
Cornea/metabolism , Drug Evaluation, Preclinical/methods , Drugs, Investigational/metabolism , High-Throughput Screening Assays , Models, Biological , Ocular Absorption , Abattoirs , Administration, Ophthalmic , Animals , Chemical Phenomena , Cornea/cytology , Corneal Stroma/cytology , Corneal Stroma/metabolism , Drugs, Investigational/administration & dosage , Drugs, Investigational/analysis , Drugs, Investigational/chemistry , Epithelium, Corneal/physiology , Humans , Hydrophobic and Hydrophilic Interactions , In Vitro Techniques , Kinetics , Permeability , Species Specificity , Sus scrofa
5.
Arch Pharm Res ; 37(7): 882-9, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24395530

ABSTRACT

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 ß-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 ß-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 ß-cyclodextrins in F7 significantly increase the drug content in the aqueous humor when compared with F3 ocuserts containing lidocaine HCl alone.


Subject(s)
Anesthesia, Local/methods , Lidocaine/administration & dosage , Lidocaine/chemical synthesis , Ocular Absorption/drug effects , Administration, Ophthalmic , Administration, Topical , Animals , Chemistry, Pharmaceutical , Drug Evaluation, Preclinical/methods , Lidocaine/metabolism , Ocular Absorption/physiology , Rabbits
6.
Drug Deliv ; 21(4): 307-14, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24134746

ABSTRACT

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.


Subject(s)
Chick Embryo/metabolism , Chorioallantoic Membrane/metabolism , Ocular Absorption , Quinoxalines/pharmacokinetics , Timolol/pharmacokinetics , Animals , Brimonidine Tartrate , Chick Embryo/drug effects , Chorioallantoic Membrane/drug effects , Drug Delivery Systems/methods , Drug Evaluation, Preclinical/methods , Ocular Absorption/drug effects , Ocular Absorption/physiology , Organ Culture Techniques , Quinoxalines/administration & dosage , Timolol/administration & dosage
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