Safety of Eosinophil-Depleting Therapy for Severe, Eosinophilic Asthma: Focus on Benralizumab.

Eosinophils play a pivotal role in the inflammatory pathology of asthma and have been the target of new biologic treatments for patients with eosinophilic asthma. Given the central role of interleukin (IL)-5 in the eosinophil lifecycle, several therapies directed against the IL-5 pathway have been developed, including the anti-IL-5 antibodies mepolizumab and reslizumab and the IL-5 receptor α (IL-5Rα)-directed cytolytic antibody benralizumab. Eosinophil-depleting therapies represent a relatively new class of asthma treatment, and it is important to understand their long-term efficacy and safety. Eosinophils have been associated with host protection and tumor growth, raising potential concerns about the consequences of long-term therapies that deplete eosinophils. However, evidence for these associations in humans is conflicting and largely indirect or based on mouse models. Substantial prospective clinical trial and postmarketing data have accrued, providing insight into the potential risks associated with eosinophil depletion. In this review, we explore the current safety profile of eosinophil-reducing therapies, with particular attention to the potential risks of malignancies and severe infections and a focus on benralizumab. Benralizumab is an IL-5Rα-directed cytolytic monoclonal antibody that targets and efficiently depletes blood and tissue eosinophils through antibody-dependent cell-mediated cytotoxicity. Benralizumab is intended to treat patients with severe, uncontrolled asthma with eosinophilic inflammation. The integrated analyses of benralizumab safety data from the phase III SIROCCO and CALIMA trials and subsequent BORA extension trial for patients with asthma, and the phase III GALATHEA and TERRANOVA trials for patients with chronic obstructive pulmonary disease, form the principal basis for this review.

In situ forming phase-inversion implants for sustained ocular delivery of triamcinolone acetonide.

The objectives of this study were to develop biodegradable poly-lactic-co-glycolic acid (PLGA) based injectable phase inversion in situ forming system for sustained delivery of triamcinolone acetonide (TA) and to conduct physicochemical characterisation including in vitro drug release of the prepared formulations. TA (at 0.5%, 1% and 2.5% w/w loading) was dissolved in N-methyl-2-pyrrolidone (NMP) solvent and then incorporated 30% w/w PLGA (50/50 and 75/25) polymer to prepare homogenous injectable solution. The formulations were evaluated for rheological behaviour using rheometer, syringeability by texture analyser, water uptake and rate of implant formation by optical coherence tomography (OCT) microscope. Phase inversion in situ forming formulations were injected into PBS pH 7.3 to form an implant and release samples were collected and analysed for drug content using a HPLC method. All formulations exhibited good syringeability and rheological properties (viscosity: 0.19-3.06 Pa.s) by showing shear thinning behaviour which enable them to remain as free-flowing solution for ease administration. The results from OCT microscope demonstrated that thickness of the implants were increased with the increase in time and the rate of implant formation indicated the fast phase inversion. The drug release from implants was sustained over a period of 42 days. The research findings demonstrated that PLGA/NMP-based phase inversion in situ forming implants can improve compliance in patient's suffering from ocular diseases by sustaining the drug release for a prolonged period of time and thereby reducing the frequency of ocular injections.

Investigation on solution-to-gel characteristic of thermosensitive and mucoadhesive biopolymers for the development of moxifloxacin-loaded sustained release periodontal in situ gels.

The objectives of present research were to develop and characterize thermosensitive and mucoadhesive polymer-based sustained release moxifloxacin in situ gels for the treatment of periodontal diseases. Poloxamer- and chitosan-based in situ gels are in liquid form at room temperature and transform into gel once administered into periodontal pocket due to raise in temperature to 37 °C. Besides solution-to-gel characteristic of polymers, their mucoadhesive nature aids the gel to adhere to mucosa in periodontal pocket for prolonged time and releases the drug in sustained manner. These formulations were prepared using cold method and evaluated for pH, solution-gel temperature, syringeability and viscosity. In vitro drug release studies were conducted using dialysis membrane at 37 °C and 50 rpm. Antimicrobial studies carried out against Aggregatibacter actinomycetemcomitans (A.A.) and Streptococcus mutans (S. Mutans) using agar cup-plate method. The prepared formulations were clear and pH was at 7.01-7.40. The viscosity of formulations was found to be satisfactory. Among the all, formulations comprising of 21% poloxamer 407 and 2% poloxamer 188 (P5) and in combination with 0.5% HPMC (P6) as well as 2% chitosan and 70% ß-glycerophosphate (C6) demonstrated an ideal gelation temperature (33-37 °C) and sustained the drug release for 8 h. Formulations P6 and C6 showed promising antimicrobial efficacy with zone of inhibition of 27 mm for A.A. and 55 mm for S. Mutans. The developed sustained release in situ gel formulations could enhance patient's compliance by reducing the dosing frequency and also act as an alternative treatment to curb periodontitis.

Clinical outcomes in patients with relapsing-remitting multiple sclerosis who switch from natalizumab to delayed-release dimethyl fumarate: A multicenter retrospective observational study (STRATEGY).

BACKGROUND: Delayed-release dimethyl fumarate (DMF) may be a therapeutic option for patients with relapsing-remitting multiple sclerosis (RRMS) who are treated with natalizumab and require a change in therapy. However, there is limited information regarding predictors of favorable treatment outcomes in patients switching from natalizumab to DMF. Clinical practices and sequencing protocols vary. Herein, we present the clinical results, including annualized relapse rate (ARR) and risk of relapse, of a phase 4 retrospective observational study of patients with RRMS who switched from natalizumab to DMF in a community practice setting (STRATEGY). METHODS: STRATEGY was performed through a single time point medical record abstraction; no study visits or procedures were required. Key inclusion criteria included age ≥ 18 years, RRMS diagnosis (McDonald criteria, 2010 revised), ≥ 12 months of continuous treatment with natalizumab monotherapy before DMF initiation, and initiation of DMF ≥ 12 months before enrollment. Patients were eligible to enroll regardless of current DMF use. RESULTS: A total of 530 patients at 45 US sites enrolled, and 506 met the inclusion criteria and were included in the modified evaluable population for analysis. Mean (SD) age at DMF initiation was 47.0 (10.9) years, with a mean (SD) of 12.7 (7.2) years since MS diagnosis. The mean (SD) duration of natalizumab treatment was 3.4 (1.9) years, and the mean (SD) washout from natalizumab discontinuation to DMF initiation (n = 502) was 101.6 (164.0) days. Overall risk of relapse 12 months after DMF initiation was 19.6%. Overall unadjusted ARR was higher during the 12 months following initiation of DMF treatment compared with the 12 months following initiation of natalizumab treatment (rate ratio, 2.32 [95% CI, 1.69-3.18]; p < 0.0001), but was lower compared with that observed in the year before initiation of natalizumab (rate ratio, 0.51 [95% CI, 0.40-0.64]; p < 0.0001). At 1 year following initiation of DMF treatment, the relapse rate was lower for patients who did not experience a relapse during 1 year following initiation of natalizumab treatment than for those who did (rate ratio for relapse rate, 0.47 [95% CI, 0.16-1.38]; p = 0.1664). The relapse rate for patients who did not relapse during natalizumab treatment was significantly lower with a washout period of ≤ 90 days as compared with a washout period of > 90 days (rate ratio for relapse rate, 0.49 [95% CI, 0.26-0.90]; p = 0.0216). A total of 42 (8%) patients reported ≥ 1 adverse event leading to DMF discontinuation during the study; the most commonly reported events were gastrointestinal disorders (n = 21; 4%). CONCLUSIONS: Results from this multicenter retrospective observational study suggest that DMF may be an effective treatment option for patients who discontinue natalizumab in routine clinical practice. ARR was lower in patients who initiated DMF within 90 days of natalizumab discontinuation compared with patients who initiated DMF after 90 days of natalizumab discontinuation. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT02159573.

Evaluation of Potential Drug-Drug Interaction Between Delayed-Release Dimethyl Fumarate and a Commonly Used Oral Contraceptive (Norgestimate/Ethinyl Estradiol) in Healthy Women.

Delayed-release dimethyl fumarate (DMF) is an oral therapy for relapsing multiple sclerosis with anti-inflammatory and neuroprotective properties. This 2-period crossover study was conducted to evaluate the potential for drug-drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 µg, ethinyl estradiol 35 µg). Forty-six healthy women were enrolled; 32 completed the study. After the lead-in period (OC alone), 41 eligible participants were randomized 1:1 to sequence 1 (OC and DMF coadministration in period 1; OC alone in period 2) or sequence 2 (regimens reversed). Mean concentration profiles of plasma norelgestromin (primary metabolite of norgestimate) and ethinyl estradiol were superimposable following OC alone and OC coadministered with DMF, with 90% confidence intervals of geometric mean ratios for area under the plasma concentration-time curve over the dosing interval and peak plasma concentration contained within the 0.8-1.25 range. Low serum progesterone levels during combined treatment confirmed suppression of ovulation. The pharmacokinetics of DMF (measured via its primary active metabolite, monomethyl fumarate) were consistent with historical data when DMF was administered alone. No new safety concerns were identified. These results suggest that norgestimate/ethinyl estradiol-based OCs may be used with DMF without dose modification.

A comprehensive review on polyelectrolyte complexes.

Global research on polyelectrolytes at a fundamental and applied level is intensifying because the advantages of sustainability are being accepted in academia and industrial research settings. During recent decades, polyelectrolytes became one of the most attractive subjects of scientific research owing to their great potential in the areas of advanced technologies. Polyelectrolytes are a type of polymer that have multitudinous ionizable functional groups. Ionized polyelectrolytes in solution can form a complex with oppositely charged polyelectrolytes - a polyelectrolyte complex (PEC). The present article provides a comprehensive review on PECs and their classification, theory and characterization, as well as a critical analysis of the current research.

Lipid based nanocarriers system for topical delivery of photosensitizers.

Topical photodynamic therapy (PDT) is a non-invasive technique used in the treatment of malignant and non-malignant skin diseases. It offers great promise because of its simplicity, enhanced patient compliance, localisation of the photosensitizer, as well as the use of light and oxygen to achieve photocytotoxicity. Despite progress in photosensitizer-mediated topical PDT, its clinical application is limited by poor penetration of photosensitizers through the skin. Therefore, much effort has been made to develop nanocarriers that can tackle the challenges of conventional photosensitizer-mediated PDT for topical delivery. This review discusses recent data on the use of different types of lipid-based nanocarriers in delivering photosensitizer for topical PDT.

Application of diverse natural polymers in the design of oral gels for the treatment of periodontal diseases.

The objective of this study was to prepare periodontal gels using natural polymers such as badam gum, karaya gum and chitosan. These gels were tested for their physical and biochemical properties and assessed for their antibacterial activity against Aggregatibacter actinomycetemcomitans and Streptococcus mutans, two pathogens associated with periodontal disease. Badam gum, karaya gum and chitosan were used to prepare gels of varying concentrations. Moxifloxacin hydrochloride, a known antimicrobial drug was choosen in the present study and it was added to the above gels. The gels were then run through a battery of tests in order to determine their physical properties such as pH and viscosity. Diffusion studies were carried out on the gels containing the drug. Antimicrobial testing of the gels against various bacteria was then carried out to determine the effectiveness of the gels against these pathogens. The results showed that natural polymers can be used to produce gels. These gels do not have inherent antimicrobial properties against A. actinomycetemcomitans and S. mutans. However, they can be used as a transport vehicle to carry and release antimicrobial drugs.

Recent Advances in Non-Invasive Delivery of Macromolecules using Nanoparticulate Carriers System.

BACKGROUND: The drug delivery of macromolecules such as proteins and peptides has become an important area of research and represents the fastest expanding share of the market for human medicines. The most common method for delivering macromolecules is parenterally. However parenteral administration of some therapeutic macromolecules has not been effective because of their rapid clearance from the body. As a result, most macromolecules are only therapeutically useful after multiple injections, which causes poor compliance and systemic side effects. METHOD: Therefore, there is a need to improve delivery of therapeutic macromolecules to enable non-invasive delivery routes, less frequent dosing through controlled-release drug delivery, and improved drug targeting to increase efficacy and reduce side effects. RESULT: Non-invasive administration routes such as intranasal, pulmonary, transdermal, ocular and oral delivery have been attempted intensively by formulating macromolecules into nanoparticulate carriers system such as polymeric and lipidic nanoparticles. CONCLUSION: This review discusses barriers to drug delivery and current formulation technologies to overcome the unfavorable properties of macromolecules via non-invasive delivery (mainly intranasal, pulmonary, transdermal oral and ocular) with a focus on nanoparticulate carrier systems. This review also provided a summary and discussion of recent data on non-invasive delivery of macromolecules using nanoparticulate formulations.

Evaluation of Antifungal Efficacy of Ethanolic Crude Lawsone and Listerine Mouthwash in Uncontrolled Diabetics and Denture Wearers - A Randomized Clinical Trial.

INTRODUCTION: Lawsonia Inermis (LI) is a shrub cultivated throughout India. Many in vitro studies have been done on antifungal activity of LI, although none of the studies have been conducted invivo. AIM: To evaluate the antifungal efficacy of ethanolic extract of crude lawsone in comparison with listerine mouth wash in known diabetics and wearing dentures. MATERIALS AND METHODS: A total of 60 subjects were taken and randomly divided into two groups of 30 each. Group 1 received crude lawsone mouthwash and Group 2 received listerine mouth wash. Oral rinse technique was performed. Each subject was given distilled water at baseline and Colony Forming Units (CFU) of candidal species was determined. Post therapeutic samples were then collected 1hr and 1week following drug usage and they were further advised to use given mouth washes twice daily with volume of 5ml/rinse for 30 seconds and CFU was evaluated. RESULTS: Crude lawsone mouthwash showed superior antifungal activity when compared to listerine mouthwash. On individual comparison of both mouth washes at baseline, 1hr and 1week highly significant results were obtained using inferential statistics. The inter group comparison was done using independent t-test where lawsone was considered to be more effective in reducing CFU, at 1hr and 1week of using the mouth wash (p<0.01). Subjective symptoms like taste and smell were determined by chi square test where good taste was felt for lawsone and olfactory satisfaction was good with listerine (p<0.01). Burning sensation was found to be more with listerine mouth wash. CONCLUSION: The present study revealed superior antifungal activity with ethanolic extract of crude lawsone mouth wash compared with listerine mouthwash.

IDENTIFICATION OF PHARMACEUTICAL EXCIPIENT BEHAVIOR OF CHICKPEA (CICER ARIETINUM) STARCH IN GLICLAZIDE IMMEDIATE RELEASE TABLETS.

In the past few years, there are number of researchers carrying out their research on the excipients derived from polysaccharides and some of these researches show that natural excipients are comparable and can serve as an alternative to the synthetic excipients. Hence, the objectives of this research are to characterize the naturally sourced chickpea starch powder and to study the pharmaceutical excipient behavior of chickpea starch in gliclazide immediate release (IR) tablets. In this research, the binding properties of chickpea starch were compared to that of povidone, whereas the disintegrant properties of chickpea starch were compared to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Flow property of chickpea starch was assessed with the measurement of bulk density, tapped density, compressibility index and angle of repose. Calibration curve for gliclazide in phosphate buffer pH 7.4 was developed. Gliclazide IR tablets were then produced with direct compression method. Physicochemical characteristics of the tablets, including thickness, tablet weight uniformity, hardness, disintegration time and friability were evaluated. Then, in vitro dissolution studies were performed by following United States Pharmacopeia (USP) dissolution method. The dissolution results were analyzed and compared with t30, t50, dissolution efficiency (DE). Lastly, drug-excipient compatibility studies, including Fourier transform infrared (FTIR) spectroscopic analysis and differential scanning calorimetric (DSC) analysis were carried out. Fair flow property was observed in the chickpea starch powder. Furthermore, the tablets produced passed all the tests in physicochemical characteristics evaluation except hardness and disintegration test. Additionally, in vitro dissolution studies show that chickpea starch acted as a disintegrant instead of a binder in gliclazide IR tablets and its disintegrant properties were comparable to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Besides that, gliclazide was also compatible with the excipients used. Chickpea starch acted as a disintegrant in gliclazide IR tablets, instead of a binder. Therefore, chickpea starch can be a promising disintegrant in gliclazide IR tablets.

Design and statistical optimization of an effervescent floating drug delivery system of theophylline using response surface methodology.

The aim of this research was to formulate effervescent floating drug delivery systems of theophylline using different release retarding polymers such as ethyl cellulose, Eudragit® L100, xanthan gum and polyethylene oxide (PEO) N12K. Sodium bicarbonate was used as a gas generating agent. Direct compression was used to formulate floating tablets and the tablets were evaluated for their physicochemical and dissolution characteristics. PEO based formulations produced better drug release properties than other formulations. Hence, it was further optimized by central composite design. Further subjects of research were the effect of formulation variables on floating lag time and the percentage of drug released at the seventh hour (D7h). The optimum quantities of PEO and sodium bicarbonate, which had the highest desirability close to 1.0, were chosen as the statistically optimized formulation. No interaction was found between theophylline and PEO by Fourier Transformation Infrared spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) studies.

Production, Characterization and Evaluation of Kaempferol Nanosuspension for Improving Oral Bioavailability.

CONTEXT: Kaempferol has a large particle size and poor water solubility, leading to poor oral bioavailability. The present work aimed to develop a kaempferol nanosuspension (KNS) to improve pharmacokinetics and absolute bioavailability. METHODS: A nanosuspension was prepared using high pressure homogenization (HPH) techniques. The physico-chemical properties of the kaempferol nanosuspension (KNS) were characterized using photon correlation spectroscopy (PCS), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR) and x-ray diffractometry (XRD). A reversephase high performance liquid chromatography (RP-HPLC) method for the analysis of the drug in rat plasma was developed and validated as per ICH guidelines. In vivo pharmacokinetic parameters of oral pure kaempferol solution, oral kaempferol nanosuspension and intravenous pure kaempferol were assessed in rats. RESULTS AND DISCUSSION: The kaempferol nanosuspension had a greatly reduced particle size (426.3 ± 5.8 nm), compared to that of pure kaempferol (1737 ± 129 nm). The nanosuspension was stable under refrigerated conditions. No changes in physico-chemical characteristics were observed. In comparison to pure kaempferol, kaempferol nanosuspension exhibited a significantly (P<0.05) increased in Cmax and AUC(0-∞) following oral administration and a significant improvement in absolute bioavailability (38.17%) compared with 13.03% for pure kaempferol. CONCLUSION: These results demonstrate enhanced oral bioavailability of kaempferol when formulated as a nanosuspension.

Formulation of Gastric Floating System Using Bio-Sourced Terminalia Catappa Gum and in vivo Evaluation.

A central composite design was applied to design a novel gastric floating drug delivery system comprising propranolol HCl in Terminalia catappa gum and to evaluate the buoyancy, in vitro drug release behavior, and pharmacokinetic parameters. All formulations exhibited good buoyancy properties in vitro reflected by floating lag time of 1-110 sec, total floating time of 9-16 h and prolonged release behaviour (upto 12 h). Statistically optimised formulation (PBGRso) was orally administered to human volunteers under both fasted and fed conditions to evaluate gastric floating behavior under different food conditions by X-ray evaluation. In vivo studies of optimised formulations revealed that the gastric residence time of floating tablets was enhanced in the fed but not in the fasted state. Pharmacokinetic studies of the optimised Terminalia catappa formulation and a commercial product (Ciplar LA 80) carried out on healthy human volunteers showed a significant improvement in the bioavailability (132%) of propranolol HCl released from from the experimental Terminalia catappa formulations compared with Ciplar LA 80.

Opportunities for Nano-Formulations in Type 2 Diabetes Mellitus Treatments.

Diabetes mellitus has been a threat to humans for many years. Amongst the different diabetes types, type 2 diabetes mellitus is the most common, and this is due to drastic changes in human lifestyle such as lack of exercise, stressful life and so on. There are a large number of conventional treatment methods available for type 2 diabetes mellitus. However, most of these methods are curative and are only applicable when the patient is highly symptomatic. Effective treatment strategies should be geared towards interfering with cellular and bio molecular mechanisms associated with the development and sustenance of the disease. In recent years, research into the medical potential of nanoparticles has been a major endeavor within the pharmaceutical industries. Nanoparticles display unique and tuneable biophysical characteristics which are determined by their shape and size. Nanoparticles have been used to manifest the properties of drugs, and as carriers for drug and vaccine delivery. Notwithstanding, there are further opportunities for nanoparticles to augment the treatment of a wide range of life threatening diseases that are yet to be explored. This review article seeks to highlight the application of potential nano-formulations in the treatment of type 2 diabetes mellitus. In addition, the activity of nanomedicine supplements in reversing insulin resistance is also discussed.

Formulation and optimization of gastric floating drug delivery system using Central composite design and its biopharmaceutical evaluation.

The present work investigates the formulation and biopharmaceutical estimation of gastric floating drug delivery system (GFDDS) of propranolol HCl using semi-synthetic polymer carboxymethyl ethyl cellulose (CMEC) and a synthetic polymer polyethylene oxide (PEO). A central composite design was applied for optimization of polymer quantity (CMEC or PEO) and sodium bicarbonate concentration as independent variables. The dependent variables evaluated were: % of drug release at 1 hr (D1hr), % drug release at 3 hr (D3hr) and time taken for 95% of drug release (t95). Numerical optimization and graphical optimization were conducted to optimize the response variables. All observed responses of statistically optimized formulations were in high treaty with predicted values. Accelerated stability studies were conducted on the optimized formulations at 40 ± 2°C/75% ± 5% RH and confirm that formulations were stable. Optimized formulations were evaluated for in vivo buoyancy characterization in human volunteers and were found buoyant in gastric fluid. Gastric residence time was enhanced in the fed but not the fasted state. The optimized formulations and marketed formulation were administered to healthy human volunteers and evaluated for pharmacokinetic parameters. Mean residence time (MRT) was prolonged and AUC levels were increased for both optimized floating tablets when compared with marketed product. High relative bioavailability obtained with optimized gastric floating tablets compared to commercial formulation, indicated the improvement of bioavailability.

Preparation and in vitro characterization of a non-effervescent floating drug delivery system for poorly soluble drug, glipizide.

The aim of the present study was to formulate a non-effervescent floating drug delivery system of glipizide, a poorly water soluble drug. The solubility of glipizide was initially enhanced using a solid dispersion (SD) strategy with the help of hydrophilic carriers such as poloxamer, cyclodextrin, and povidone. The optimized core material/SD was further formulated into non-effervescent floating tablets (NEFT) by using matrix ballooning inducers, such as crospovidone and release retarding agents including HPMC and PEO. Poloxamer-based solid dispersions prepared by a solvent evaporation technique showed the highest dissolution rate (1 : 10 drug to carrier ratio) compared with all other dispersions. NEFT were evaluated for all physico-chemical properties including in vitro buoyancy, dissolution, and release rate. All of the tablets were found to be within pharmacopoeial limits and all of the formulations exhibited good floating behavior. The formulations (F2 and F3) were optimized based on their 12 h drug retardation with continuous buoyancy. The optimized formulations were characterized using FTIR and DSC and no drug and excipient interaction was found. In-vitro buoyancy and dissolution studies showed that non-effervescent floating drug delivery systems provide a promising method of achieving prolonged gastric retention time and improved bioavailability of glipizide.

Investigation on antidiarrhoeal activity of Aristolochia indica Linn. Root extracts in mice.

BACKGROUND: The present study aimed at investigating the effect of ethanolic extract (EtAI), and aqueous extract (AqAI) of Aristolochia indica Linn roots on castor oil-induced diarrhoea and study on small intestinal transit. Phytochemical analysis of extracts was performed as per standard procedure. MATERIALS AND METHODS: The oral toxicity study using Swiss albino mice was performed in accordance with OECD guidelines. The EtAI and AqAI extracts of Aristolochia indica Linn were studied for antidiarrhoeal property using castor oil-induced diarrhoeal model and charcoal-induced gastrointestinal motility test in Swiss albino mice. RESULTS: Among the tested doses of 200 and 400 mg/kg body weight, the extracts reduced the frequency and severity of diarrhoea in test animals throughout the study period. At the same doses, the extract delayed the intestinal transit of charcoal meal in test animals as compared to the control and the results were statistically significant. CONCLUSION: Experimental findings showed that ethanol extract of Aristolochia indica Linn root possess significant antidiarrheal activity and may be a potent source of anti-diarrhoeal drug in future.

Preparation and in vitro characterization of non-effervescent floating drug delivery system of poorly soluble drug, carvedilol phosphate.

The objective of the study was to enhance the solubility of carvedilol phosphate and to formulate it into non-effervescent floating tablets using swellable polymers. Solid dispersions (SD) of carvedilol were prepared with hydrophilic carriers such as polyvinylpyrrolidone and poloxamer to enhance solubility. Non-effervescent floating tablets were prepared with a combination of optimized solid dispersions and release retarding polymers/swellable polymers such as xanthan gum and polyethylene oxide. Tablets were evaluated for physicochemical properties such as hardness, thickness and buoyancy. SD prepared with the drug to poloxamer ratio of 1:4 by melt granulation showed a higher dissolution rate than all other dispersions. Formulations containing 40 mg of polyethylene oxide (C-P40) and 50 mg xanthan gum (C-X50) were found to be best, with the drug retardation up to 12 hours. Optimized formulations were characterized using FTIR and DSC and no drug and excipient interactions were detected.

Formulation of gastroretentive floating drug delivery system using hydrophilic polymers and its in vitro characterization

The aim of the present research is to formulate and evaluate the gastroretentive floating drug delivery system of antihypertensive drug, propranolol HCl. Gastroretentive floating tablets (GRFT) were prepared by using a synthetic hydrophilic polymer polyethylene oxide of different grades such as PEO WSR N-12 K and PEO 18 NF as release retarding polymers and calcium carbonate as gas generating agent. The GRFT were compressed by direct compression strategy and the tablets were evaluated for physico-chemical properties, in vitro buoyancy, swelling studies, in vitro dissolution studies and release mechanism studies. From the dissolution and buoyancy studies, F 9 was selected as an optimized formulation. The optimized formulation followed zero order rate kinetics with non-Fickian diffusion mechanism. The optimized formulation was characterised with FTIR studies and observed no interaction between the drug and the polymers.

O objetivo da presente pesquisa é o de formular e avaliar o sistema de liberação de fármaco gastrorretentivo flutuante, contendo o anti-hipertensivo, cloridrato de propranolol. Comprimidos gastrorretentivo flutuantes (GRFT) foram preparados utilizando um polímero hidrofílico sintético, o óxido de polietileno, de diferentes graus, tais como GE WSR N-12 K e GE 18 NF, como polímeros de retardamento de liberação, e carbonato de cálcio, como agente gerador de gases. Os GRFT foram comprimidos por compressão direta e avaliados para determinação das propriedades físico-químicas, flutuabilidade in vitro, estudos de inchamento, de dissolução in vitro e de mecanismo de liberação. Dos testes de dissolução e de flutuabilidade, selecionou-se F 9 como formulação otimizada. A formulação otimizada seguiu cinética de ordem zero, com mecanismo de difusão não-Fickiano. Essa formulação foi caracterizada por estudos de FTIR, não se observando interação entre o fármaco e os polímeros.