Enhanced oral delivery of risperidone through a novel self-nanoemulsifying powder (SNEP) formulations: in-vitro and ex-vivo assessment.

CONTEXT: The oral delivery of risperidone encounters a number of problems, such as pH dependent solubility and low bioavailability, due to its lipophilicity and aqueous insolubility. OBJECTIVE: To improve the solubility, dissolution and intestinal permeation thereby bioavailability of risperidone through a novel self-nanoemulsifying powder (SNEP) formulations. MATERIALS AND METHODS: Oleic acid, Tween® 20, PEG 600 and Aerosil® 200 were chosen as oil, surfactant, co-surfactant and carrier, respectively from solubility and emulsification studies. Ternary phase diagram was constructed to determine emulsifying region. RESULTS AND DISCUSSION: The Z-average and polydispersity Index of developed formulation was 83.1 nm and 0.306, respectively. Ex vivo permeation studies on isolated rat intestine indicated that the amount of risperidone permeated from SNEP formulation was increased around 4- and 1.8-fold than that of pure drug and marketed formulation, respectively. CONCLUSION: This developed SNEP formulations can be regarded as novel and commercially feasible alternative to the current risperidone formulations.

A pH-triggered delayed-release chronotherapeutic drug delivery system of aceclofenac for effective management of early morning symptoms of rheumatoid arthritis.

CONTEXT: Rheumatoid arthritis (RA) is differentiated as an early morning exacerbation of the core arthritis condition associated with increase in pain and stiffness in joints and necessitate for medication. OBJECTIVE: The aim of the present work was to develop and optimise a pH-triggered delayed-release colon-specific aceclofenac microspheres and to accomplish chronotherapy of RA. METHODS: A 3-factor, 3-level Box-Behnken design (BBD) was used to optimise selected variables. Developed formulation was evaluated for in vivo delayed response and anti-arthritis activity in rats. RESULTS: The particle size and encapsulation efficacy of these microspheres were 117.36 ± 10.54 µm and 85.06 ± 5.85%, respectively. Optimised formulation was analysed by SEM, DSC, X-RPD and FTIR. The in vivo evaluation revealed delayed anti-inflammatory activity in carrageenan-induced rats and anti-arthritic activity in freund's adjuvant-induced arthritis rats. CONCLUSION: The optimised aceclofenac microspheres formulation is potential for the chronotherapy of early morning symptoms of RA.

Improved anti-diabetic activity of glibenclamide using oral self nano emulsifying powder.

The objective of the present study was to improve solubility, dissolution rate and therapeutic efficacy of a BCS Class II drug, glibenclamide by using oral self nano emulsifying powder. The powder was prepared by adsorbing the mixture of oil, surfactant and co-surfactant onto a carrier with large surface area; Aerosil 200. The ratios of oil and Smix (surfactant/co-surfactant mixture) required to produce an emulsion was optimized based on percentage transmittance studies and particle size determinations. The optimized formulation was subjected to in vitro dissolution study and in vivo therapeutic efficacy in rabbits by monitoring blood glucose levels. Scanning electron microscopy, differential scanning calorimetry and X-ray powder diffraction studies revealed that the drug was present in amorphous form in the final formulation. The in vivo study in rabbits indicated the improved therapeutic efficacy of glibenclamide in self-nanoemulsifying powder compared to plain drug.

Solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of glimepiride: development and antidiabetic activity in albino rabbits.

CONTEXT: This study presents novel self-nanoemulsifying drug delivery system potential of oral delivering which leads poorly aqueous soluble drug glimepiride. OBJECTIVE: The objective of this study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) for the improved oral delivery of glimepiride and to evaluate its therapeutic efficacy in albino rabbits. RESULTS AND DISCUSSION: The droplet size analyses revealed a droplet size of less than 200 nm. The solid state characterization of S-SNEDDS by scanning electron microscopy (SEM), X-ray powder diffraction and differential scanning calorimetry (DSC) revealed the absence of crystalline glimepiride in the S-SNEDDS. The in vitro dissolution studies revealed that the significant improvement in glimepiride release characteristics. The effect of S-SNEDDS on therapeutic efficacy of glimepride was assessed in albino rabbits by monitoring blood glucose levels and compared with free drug suspension, L-SNEDDS. The S-SNEDDS showed significant (p < 0.05) increase in in vitro drug release and therapeutic efficacy as compared with free drug. CONCLUSION: This study demonstrated that S-SNEDDS is a promising novel drug delivery system of glimepride to enhance oral delivery.

Enhancement of solubility, dissolution release profile and reduction in ulcerogenicity of piroxicam by inclusion complex with skimmed milk.

CONTEXT: Piroxicam (PXM), a non-steroidal anti-inflammatory drug which is poorly soluble in water and ulcerogenic. Milk has been used against the gastric disturbances caused by non-steroidal anti-inflammatory drugs. In this study, skimmed milk (SKM) is used as the carrier for inclusion complex (IC) due to its surface active agent and amino acid content. PURPOSE: To enhance the solubility, dissolution rate and prevent ulcerogenicity of PXM though IC with SKM. METHODS: IC of PXM were prepared with SKM by solvent evaporation method using rota evaporator and were evaluated for solubility, dissolution, solid state characterization, drug excipient interaction, rat intestinal permeation, ulcerogenicity and histopathological studies. RESULTS: Solubility of PXM was enhanced 2.5 times with IC. The dissolution release and amount of PXM permeated through rat small intestine was enhanced significantly with IC. Decreases in the gastric lesion index values of IC were observed than physical mixture (PM) and free PXM. The histopathological studies revealed significant reduction in ulceration in rat stomach after treatment with IC. CONCLUSION: It is concluded that SKM is a good carrier to prepare IC of PXM for oral administration.

Resident compliance with the american academy of ophthalmology preferred practice pattern guidelines for primary open-angle glaucoma.

PURPOSE: To examine resident adherence to preferred practice pattern (PPP) guidelines set up by the American Academy of Ophthalmology for follow-up care of primary open-angle glaucoma (POAG) patients. DESIGN: Retrospective chart review. PARTICIPANTS: One hundred three charts were selected for analysis from all patients with an International Classification of Diseases, Ninth Revision, code of open-angle glaucoma or its related entities who underwent a follow-up evaluation between July 2, 2003, and December 15, 2004, at the resident ophthalmology clinic in the Durham Veteran Affairs Medical Center. METHODS: Follow-up visits of POAG patients were evaluated for documentation of 19 elements in accordance to PPP guidelines. MAIN OUTCOME MEASURES: Compliance rates for the 19 elements of PPP guidelines first were averaged in all charts, and then were averaged per resident and were compared among 8 residents between their first and second years of residency. RESULTS: The overall mean compliance rate for all 19 elements was 82.6% for all charts (n = 103), 78.8% for first-year residents, and 81.7% for second-year residents. The increase from first to second year of residency was not significant (P>0.05). Documentation rates were high (>90%) for 14 elements, including all components of the physical examination and follow-up as well as most components of the examination history and management plan. Residents documented adjusting target intraocular pressure downward, local or systemic problems with medications, and impact of visual function on daily living approximately 50% to 80% of the time. Documentation rates for components of patient education were the lowest, between 5% and 16% in all charts. CONCLUSIONS: Residents' compliance with PPP guidelines for a POAG follow-up visit was very high for most elements, but documentation rates for components of patient education were poor. Adherence rates to PPP guidelines can be used as a tool to evaluate and improve resident performance during training. However, further studies are needed to establish the advantages of using PPP guidelines for resident education and to determine if such assessments can lead to improved patient care.

Optimization and characterization of gastroretentive floating drug delivery system using Box-Behnken design.

CONTEXT: One among many strategies to prolong gastric residence time and improve local effect of the metronidazole in stomach to eradicate Helicobacter pylori in the treatment of peptic ulcer was floating drug delivery system particularly effervescent gastroretentive tablets. OBJECTIVE: The objective of this study was to prepare and evaluate, effervescent floating drug delivery system of a model drug, metronidazole. METHODS: Effervescent floating drug delivery tablets were prepared by wet granulation method. A three-factor, three levels Box-Behnken design was adopted for the optimization. The selected independent variables were amount of hydroxypropyl methylcellulose K 15M (X1), sodium carboxy methylcellulose (X2) and NaHCO3 (X3). The dependent variables were floating lag time (YFLT), cumulative percentage of metronidazole released at 6th h (Y6) and cumulative percentage of metronidazole released at 12th h (Y12). Physical properties, drug content, in vitro floating lag time, total floating time and drug release behavior were assessed. RESULTS: YFLT range was found to be from 1.02 to 12.07 min. The ranges of other responses, Y6 and Y12 were 25.72 ± 2.85 to 77.14 ± 3.42 % and 65.47 ± 1.25 to 99.65 ± 2.28 %, respectively. Stability studies revealed that no significant change in in vitro floating lag time, total floating time and drug release behavior before and after storage. CONCLUSION: It can be concluded that a combination of hydroxypropyl methylcellulose K 15M, sodium carboxy methylcellulose and NaHCO3 can be used to increase the gastric residence time of the dosage form to improve local effect of metronidazole.

Influence of actin cytoskeletal integrity on matrix metalloproteinase-2 activation in cultured human trabecular meshwork cells.

PURPOSE: The goal of this study was to investigate the possible link between actin cytoskeletal integrity and the activation of matrix metalloproteinases (MMPs) in trabecular meshwork (TM) cells. METHODS: Primary human TM (HTM) cells treated with different actin cytoskeleton-interfering agents, including cytochalasin D, latrunculin A, ethacrynic acid (ECA), a Rho kinase inhibitor (Y-27632), and H-7 (serine/threonine kinase inhibitor), were examined for changes in actin cytoskeletal organization by phalloidin staining, MMP-2 activation by gelatin zymography, expression of MT1-MMP by quantitative real-time PCR analysis, levels of tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2), and activation of p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated protein kinase (ERK) by immunoblotting. RESULTS: Treatment of HTM cells with cytochalasin D and latrunculin A led to significant activation of MMP-2, p38 MAPK, and ERK1/2, which appeared to correlate with changes in cell morphology and actin depolymerization. Additionally, treatment with these cytoskeleton-disrupting agents elicited increased expression of MT1-MMP in HTM cells, concomitant with a decrease in the levels of secreted TIMP-1 and TIMP-2. In contrast, treatment with ECA, Y-27632, or H-7 triggered changes in cell shape and reduced actin stress fibers in HTM cells but did not exert significant effects on MMP-2 activation or MT1-MMP expression. CONCLUSIONS: These studies indicate that cytochalasin D- and latrunculin A-induced alteration of actin cytoskeletal integrity in HTM cells is associated with MMP-2 activation, most likely through the upregulation of its activator, MT1-MMP. These data provide a mechanistic connection between actin cytoskeletal organization and MMP-2 activation in TM cells and offer new insights into extracellular matrix remodeling in the aqueous outflow pathway.