Factors associated with appropriate inhaler use in patients with COPD - lessons from the REAL survey

The authors thank Clarice Field (PhD) and Paul McKiernan (PhD) of Novartis for providing medical writing support, which was funded by Novartis AG, Basel, Switzerland, in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). Pankaj Goyal and Joao Mendes, Novartis Pharma AG, Basel, contributed to the design and conceptualization of study. The survey was designed by PDD, London, United Kingdom, and GfK Switzerland AG, Basel, Switzerland. The survey was conducted by GfK Switzerland AG, Basel, Switzerland, and sponsored by Novartis Pharma AG, Basel, Switzerland.Peer reviewedPublisher PD

FORMULATION AND EVALUATION OF SYNTHESIZED QUINAZOLINONE DERIVATIVE FOR COLON SPECIFIC DRUG DELIVERY

ABSTRACTObjective: The current research deals with the formulation and evaluation of synthesized quinazolinone derivative for colon site specific delivery.Methods: The synthesized quinazolinone derivative was enteric coated 5% Eudragit L-100 with by wet granulation method using guar gum, pectin,and guar gum pectin combination as hydrophilic polymer. The prepared matrix tablet was characterized by differential scanning calorimetry andevaluated for different pre-compression and post-compression studies and drug release profiles.Results: All the matrix tablets were within the range of pharmacopeial limits with better flow properties. All the six formulations of matrix tablets haddisintegrated within 5-6 minutes. The optimized formulation selected was F6 formulation combination of guar gum and pectin with 95.79% of drugrelease than compared to the remaining formulation. The optimized matrix tablets followed zero order kinetics with Fickian diffusion.Conclusion: The results proposed that the combination of guar gum and pectin coated tablet with 5% Eudragit L-100 of synthesized quinazolinonederivative is a promising colon site specific delivery.Keywords: Quinazolinone derivative, In vitro drug release, Disintegration time, Guar gum, Pectin, 5% Eudragit L-100, Colon site-specific delivery, Wetgranulation, Compression

FORMULATION AND EVALUATION OF NOVEL CHROMENE DERIVATIVE AS AN ANTI INFLAMMATORY AGENT USED FOR IBD

Objective: To formulate and evaluate an extended-release (ER) tablet of a new molecule, 2-amino-4-(4-bromophenyl)-7-hydroxy-4H-chromene-3- carbonitrile using a combination of two polymers (hydroxypropyl methyl cellulose [HPMC] K100 and HPMC phthalate) which control the rate and degree of the drug release through 12 hrs period and protect the drug release from acidic pH.Methods: Five batches of tablets (4HC1, 4HC2, 4HC3, 4HC4, 4HC5) were produced by direct compression method. Morphological evaluation of the powder blend was carried out by differential scanning calorimetry and Powered X-ray diffractometry. The evaluation studies such as flow properties, hardness, friability, drug content, and release study were conducted according to pharmacopoeial standards.Results: The physicochemical characteristics of all the granules and tablets were generally satisfactory. The drug release followed zero order, Higuchi model kinetics with diffusion and dissolution mediated mechanism. Tablets were evaluated for physicochemical parameters and promising. Stability studies indicated the dosage form is stable for 3 months at accelerated conditions.Conclusion: From the results received from all test, it was concluded that formulation 4HC4 are the most suitable choice for developing 12 hrs ERtablets. This finding reveals that a particular concentration of HPMC K100 was capable of producing ER.Keywords: Chromene derivative, Extended-release, Hydroxypropyl methylcellulose phthalate, Hydroxypropyl methylcellulose K100

DESIGN AND INVITRO CHARACTERIZATION OF METFORMIN LOADED RESEALED ERYTHROCYTES

Objective: Metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes. Theobjective of this study was to retard the release of metformin using carrier erythrocyte for getting a parenteral slow release depot formulation.Methods: The study retards the release of metformin by encapsulating in carrier erythrocyte. Endocytosis is the method used for the encapsulationof the drug metformin.Results: The optimized formulation shows 98.34% of drug release within 12 days. From the in vitro release data, zero order kinetic graph shows thebest fit graph. % cell recovered was found to be 73-78% and it suggests that the loading technique was less destructive.Conclusion: The optimized formulation is a perfect carrier for the parenteral slow release depot of metformin.Keywords: Resealed erythrocytes, Cross-linking, Cell recovery, Endocytosis, Slow release depot formulation

DEVELOPMENT AND IN VITRO EVALUATION OF NANOLIPID CARRIERS OF CLOBETASOL PROPIONATE AND PRAMOXINE HYDROCHLORIDE FOR TOPICAL DELIVERY

Objective: Formulation and characterization of clobetasol propionate (CP) and pramoxine hydrochloride (PH) loaded nanostructured lipid carriers (NLC) offering improved performance in terms of drug loading and long-term stability for topical drug delivery. Methods: Drug-loaded NLC formulation was designed by melt-emulsification ultrasonication technique, by fluctuating the concentration of stearic acid and oleic acid. Poloxamer F68 and tween 80 were used as surfactants in the formulation and soya lecithin was used as stabilizer and co-surfactant. Differential scanning calorimetry (DLS), scanning electron microscopic studies (SEM), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), x-ray diffraction (XRD), are the techniques used to characterize the preparations. Optimized drug-loaded formulations were evaluated for particle size, zeta potential, entrapment efficiency, in vitro drug release, hemocompatibility assay and cytotoxicity screening. Results: For drug loaded formulation the particle size was found in nanometric range. In vitro drug release was carried out using dialysis membrane and drug release after 24h was found to be 90.98 %±1.89 for CP and 79.81 %±4.20 for PH. Conclusion: The formulated NLC is a potential approach for sustained release of drug which may reduce systemic side effects, increase skin retention time and duration of action. Further in vivo studies will confirm the effect of NLC to increase skin retention time, decreases systemic absorption of the corticosteroid thereby avoiding side effects

Enhanced Lymphatic Uptake of Leflunomide Loaded Nanolipid Carrier via Chylomicron Formation for the Treatment of Rheumatoid Arthritis

Purpose: The current study aims the lymphatic delivery of leflunomide loaded nanostructured lipid carriers (LNLC) for the treatment of rheumatoid arthritis, mainly focussed to enhance the lymphatic delivery via chylomicron formation, improved bioavailability and reduced systemic toxicity. Methods: Melt emulsification ultra-sonication method was used to formulate the nanostructured lipid carrier (NLC) containing leflunomide. Four batches were prepared by using various concentration of surfactants (tween 80 and poloxmer 188) and lipid mixtures (stearic acid and oleic acid). All the formulations were studied for various physiochemical properties Results: The formulation with increased concentration of lipid and surfactants showed highest entrapment efficiency (93.96 ± 0.47%) and better drug release (90.35%) at the end of 48 hrs. In vivo tests were carried out to determine the antiarthritic potential of the formulation in Sprague-dawley rats for a duration of 30d. The effect was evaluated by measuring the reduction in knee thickness. LNLC showed a marked reduction in inflammation compared to standard drug. Intestinal lymphatic uptake studies of LNLC were performed by intraduodenal administration and compared with leflunomide drug solution. The mesenteric lymph node was analysed by HPLC method and the concentration of drug was estimated. It showed that LNLC having highest uptake (40.34μg/ml) when compared with leflunomide drug solution (10.04μg/ml). Radiographic analysis and histopathological studies showed the formation of healthy cartilage after treatment period. Conclusion: The results suggested that LNLC has the potential to reduce the systemic toxicities associated with conventional therapy along with improved efficacy in the treatment of rheumatoid arthritis

Modulation of immune response by nanoparticle-based immunotherapy against food allergens

The increasing prevalence of food allergies worldwide and the subsequent life-threatening anaphylactic reactions often have sparse treatment options, providing only symptomatic relief. Great strides have been made in research and in clinics in recent years to offer novel therapies for the treatment of allergic disorders. However, current allergen immunotherapy has its own shortcomings in terms of long-term efficacy and safety, due to the local side effects and the possibility of anaphylaxis. Allergen-specific immunotherapy is an established therapy in treating allergic asthma, allergic rhinitis, and allergic conjunctivitis. It acts through the downregulation of T cell, and IgE-mediated reactions, as well as desensitization, a process of food tolerance without any allergic events. This would result in a protective reaction that lasts for approximately 3 years, even after the withdrawal of therapy. Furthermore, allergen-specific immunotherapy also exploits several routes such as oral, sublingual, and epicutaneous immunotherapy. As the safety and efficacy of allergen immunotherapy are still under research, the exploration of newer routes such as intra-lymphatic immunotherapy would address unfulfilled needs. In addition, the existence of nanoparticles can be exploited immensely in allergen immunotherapy, which would lead to safer and efficacious therapy. This manuscript highlights a novel drug delivery method for allergen-specific immunotherapy that involves the administration of specific allergens to the patients in gradual increasing doses, to induce desensitization and tolerance, as well as emphasizing different routes of administration, mechanism, and the application of nanoparticles in allergen-specific immunotherapy

Formulation and Optimization of Clotrimazole-Loaded Proniosomal Gel Using 32 Factorial Design

The main aim of the study was to develop and statistically optimize the proniosomal gel for enhanced transdermal delivery using 32 factorial designs to investigate the influence of both non-ionic surfactant and cholesterol to maximize the entrapment efficiency and flux. The concentration of non-ionic surfactant and cholesterol were taken as independent variables, while entrapment efficiency and flux were taken as dependent variables. The study showed that the entrapment efficiency depends on both cholesterol and surfactant, whereas permeation flux depends only on the surfactant. Proniosomal gel showed a significantly enhanced drug permeation through the skin, with an enhancement ratio 3.81±1.85 when compared to the drug solution. Comparative evaluation of permeation studies and the in vitro release study of optimized proniosomal gel (F5) with that of marketed gel and carbopol gel showed that the penetration of the optimized formulation was enhanced 1.75 times in comparison with that of the marketed formulation, and the release was in a controlled manner. Similarly, the anticandidial activity showed a significantly higher activity (p<0.05) than the marketed and carbopol gel. This may be due to the enhanced penetration of noisome-containing drug through the fungal cell wall, inhibiting the ergo sterol synthesis, thereby causing the fungal cell death due to the presence of penetration enhancer. The stability study at two different temperatures (30 ± 2°C and 4 ± 2°C) confirmed that the formulations were stable even at the end of 45 days. Hence, proniosomal gel is an efficient carrier for the delivery of clotrimazole, thereby prolonging the action