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 & dosageABSTRACT
OBJECTIVE: The research aimed to evaluate the anti-Shigella and antacid activities of the methanolic extract of Limnophila indica. METHODS: The whole plant of L. indica was extracted using methanol and then subjected to preliminary chemical screening. The in vitro antibacterial screening on two Gram-positive and two Gram-negative bacteria as well as three Shigella species of which two bacteria were antibiotic-resistant were evaluated by disc diffusion method. Castor oil-induced diarrhoea on Wistar albino rats was performed by using loperamide as a standard control. The in vitro antacid activity was tested by artificial stomach model. The neutralization efficiency, capacity, volume and hydrogen ions consumed were also evaluated. RESULTS: The preliminary chemical screening on methanolic extract of L.indica showed the presence of phenolic compounds, flavonoids, alkaloids, fats and oils. It was proved to be a potent antibacterial agent against the four bacterial strains. Screening against Shigella species revealed that it was a powerful antibacterial agent towards antibiotic-resistant Shigella species. In the case of in vivo antidiarrheal activity, the plant has shown a dose-dependent activity and the lowest dose at 100 mg/kg gave a much better result than loperamide (P<0.01). The in vitro antacid study showed a mild activity. CONCLUSION: As the plant L. indica has been proved to be a competent antibacterial as well as a compelling antidiarrheal agent with mild antacid activity, this plant can be very well suggested to be an eminent substitute for the various synthetic anti-dysentery and antidiarrheal agents available in the market.