The release of nicotine from chewing gum formulations

The first clinically proven nicotine replacement product to obtain regulatory approval was Nicorette® gum. It provides a convenient way of delivering nicotine directly to the buccal cavity, thus, circumventing 'first-pass' elimination following gastrointestinal absorption. Since launch, Nicorette® gum has been investigated in numerous studies (clinical) which are often difficult to compare due to large variations in study design and degree of sophistication. In order to standardise testing, in 2000 the European Pharmacopoeia introduced an apparatus to investigate the in vitro release of drug substances from medical chewing gum. With use of the chewing machine, the main aims of this project were to determine factors that could affect release from Nicorette® gum, to develop an in vitro in vivo correlation and to investigate formulation variables on release of nicotine from gums. A standard in vitro test method was developed. The gum was placed in the chewing chamber with 40 mL of artificial saliva at 37'C and chewed at 60 chews per minute. The chew rate, the type of dissolution medium used, pH, volume, temperature and the ionic strength of the dissolution medium were altered to investigate the effects on release in vitro. It was found that increasing the temperature of the dissolution media and the rate at which the gums were chewed resulted in a greater release of nicotine, whilst increasing the ionic strength of the dissolution medium to 80 mM resulted in a lower release. The addition of 0.1 % sodium Jauryl sulphate to the artificial saliva was found to double the release of nicotine compared to the use of artificial saliva and water alone. Although altering the dissolution volume and the starting pH did not affect the release. The increase in pH may be insufficient to provide optimal conditions for nicotine absorption (since the rate at which nicotine is transported through the buccal membrane was found to be higher at pH values greater than 8.6 where nicotine is predominately unionised). Using a time mapping function, it was also possible to establish a level A in vitro in vivo correlation. 4 mg Nicorette® gum was chewed at various chew rates in vitro and correlated to an in vivo chew-out study. All chew rates used in vitro could be successfully used for IVIVC purposes, however statistically, chew rates of 10 and 20 chews per minute performed better than all other chew rates. Finally a series of nicotine gums was made to investigate the effect of formulation variables on release of nicotine from the gum. Using a directly compressible gum base, in comparison to Nicorette® the gums crumbled when chewed in vitro, resulting in a faster release of nicotine. To investigate the effect of altering the gum base, the concentration of sodium salts, sugar syrup, the form of the active drug, the addition sequence and the incorporation of surfactant into the gum, the traditional manufacturing method was used to make a series of gum formulations. Results showed that the time of addition of the active drug, the incorporation of surfactants and using different gum base all increased the release of nicotine from the gum. In contrast, reducing the concentration of sodium carbonate resulted in a lower release. Using a stronger nicotine ion-exchange resin delayed the release of nicotine from the gum, whilst altering the concentration of sugar syrup had little effect on the release but altered the texture of the gum.

Preformulation studies on grewia gum as a formulation excipient

Grewia gum is a naturally occurring polysaccharide which has potential as a pharmaceutical excipient. Differential scanning calorimetry and Fourier transform infrared (FT-IR) spectroscopy techniques were used to examine the thermal and molecular behaviours, respectively, of mixtures of grewia gum with cimetidine, ibuprofen or standard excipients, to assess potential interactions. No disappearance or broadening of the melting endotherm was seen with cimetidine or ibuprofen. Similarly, there was no interaction between grewia gum and the standard excipients tested. The results obtained using thermal analyses were supported by FT-IR analysis of the material mixtures. Grewia gum is an inert natural polymer which can be used alone or in combination with other excipients in the formulation of pharmaceutical dosage forms. © 2011 Akadémiai Kiadó, Budapest, Hungary.

Grewia gum 1:some mechanical and swelling properties of compact and film

Purpose: To study the mechanical and dynamic swelling properties of grewia gum, evaluate its compression behaviour and determine the effect of drying methods on its properties. Methods: Compacts (500 mg) of both freeze-dried and air-dried grewia gum were separately prepared by compression on a potassium bromide (KBr) press at different pressures and subjected to Heckel analysis. Swelling studies were performed using 200 mg compacts of the gum (freeze-dried or air-dried) compressed on a KBr press. The mechanical properties of the films of the gum prepared by casting 1 % dispersions of the gum were evaluated using Hounsfield tensiometer. The mechanical properties of grewia gum films were compared with films of pullulan and guar gum which were similarly prepared. The effect of temperature on the water uptake of the compacts was studied and the data subjected to Schott's analysis. Results: Drying conditions had no effect on the yield pressure of the gum compacts as both air-dried and freeze-dried fractions had a yield pressure of 322.6 MPa. The plots based on Schott's equation for the grewia gum samples showed that both samples (freeze-dried and air-dried) exhibited long swelling times. Grewia gum film had a tensile strength of 19.22±3.61 MPa which was similar to that of pullulan films (p > 0.05). It had an elastic modulus of 2.13±0.12 N/mm2 which was significantly lower (p < 0.05) than those of pullulan and guar gum with elastic moduli of 3.33±0.00 and 2.86±0.00 N/mm2, respectively. Conclusion: The type of drying method used does not have any effect on the degree of plasticity of grewia gum compacts. Grewia gum obtained by either drying method exhibited extended swelling duration. Matrix tablet formulations of the gum will likely swell slowly and promote sustained release of drug. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City.

Grewia gum 2:mucoadhesive properties of compacts and gels

Purpose: To compare the mucoadhesive performance of grewia polysaccharide gum with those of guar gum, carboxymethylcellulose, hydroxypropyl methylcellulose and carbopol 971P. Methods: Grewia polysaccharide gum compacts or gels as well as those of guar gum, carboxymethylcellulose, hydroxypropyl methylcellulose or carbopol 971P were prepared. Texturometric and tensile analysis of the polymer gels and compacts were carried out using a software-controlled penetrometre, TA.XTPlus texture analyzer. The polymer gels were evaluated for hardness, stickiness, work of cohesion and work of adhesion. Furthermore, the detachment force of the polymer compacts from a mucin substrate was evaluated. Results: The work of adhesion of guar gels was significantly greater than that of grewia gels (p < 0.001) but the latter showed a significantly greater work of adhesion than carboxymethylcellulose gels (p < 0.05) and hydroxypropyl methylcellulose gels (p < 0.001). However, the work of cohesion for grewia/mucin gel mixture was significantly greater (p < 0.001) than those of carboxymethylcellulose/mucin, hydroxypropyl methylcellulose/mucin and carbopol 971P/mucin gel blends. The difference between the mucoadhesive performance of grewia compacts and those of hydroxypropyl methylcellulose and carbopol 971P compacts was insignificant (p > 0.05). Conclusion: Grewia polysaccharide gum demonstrated good mucoadhesive properties, comparable to those of carbopol 971P, carboxymethylcellulose, guar gum and hydroxypropyl methylcellulose, and therefore, should be suitable for the formulation of retentive drug delivery devices. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City.

Physicochemical characterization of grewia polysaccharide gum:effect of drying method

Grewia polysaccharide gum, a potential pharmaceutical excipient was extracted from the inner stem bark of Grewia mollis, thereupon drying was achieved by three techniques: air-drying, freeze-drying and spray-drying. Analysis of the monosaccharide composition including 1H and 13C NMR spectroscopic analysis of the polysaccharide gum was carried out. The effect of the drying methods on the physicochemical properties of the gum was evaluated by Fourier transformed infra-red (FT-IR) spectroscopy, solid-state 13C nuclear magnetic resonance (NMR) spectroscopy, X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis, differential scanning calorimetry and gel permeation chromatography. Monosaccharide sugar analysis revealed that the gum is composed of glucose, rhamnose, galactose, arabinose and xylose as the main neutral sugars. These were supported by the results from 1H and 13C NMR spectroscopic analysis. FT-IR and solid-state NMR results indicated that drying technique has little effect on the structure of the polysaccharide gum but XPS showed that surface chemistry of the gum varied with drying methods. Thermogravimetric analyses showed that oxidation onset varied according to the drying method. The molecular weight was also dependent on the drying technique. For industrial extrapolation, air-drying may be preferable to spray-drying and freeze-drying when relative cost, product stability and powder flow are required, for example in tablet formulation. © 2010 Elsevier Ltd. All rights reserved.

Characterization of Grewia gum, a potential pharmaceutical excipient

Grewia gum was extracted from the inner stem bark of Grewia mollis and characterized by several techniques such as gas chromatography (GC), gel permeation chromatography (GPC), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and thermogravimetric analysis of the extracted sample. Spectroscopic techniques such as x-ray photoelectron spectroscopy (XPS), fourier-transformed infrared (FT-IR), solid-state nuclear magnetic resonance (NMR), and 1H and 13C NMR techniques were also used to characterize the gum. The results showed that grewia gum is a typically amorphous polysaccharide gum containing glucose, rhamnose, galactose, arabinose and xylose as neutral sugars. It has an average molecular weight of 5925 kDa expressed as the pullulan equivalent. The gum slowly hydrated in water, dispersing and swelling to form a highly viscous dispersion exhibiting pseudoplastic flow behaviour. The polysaccharide gum is thermally stable and may have application as stabilizer or suspending agent in foods, cosmetics and in pharmaceuticals. It may have application as a binder or sustained-release polymer matrix in tablets or granulations. © IPEC-Americas Inc.

Lily with bubble gum

General note: Title and date provided by Bettye Lane.

Development of the edible blend films with good mechanical and barrier properties from pea starch and guar gum

The individual and interactive impacts of guar gum and glycerol on the pea starch-based edible film characteristics were examined using three factors with three level Box–Behnken response surface design. The results showed that density and elongation at break were only significantly (p < 0.05) affected by pea starch and guar gum in a positive linear fashion. The quadratic regression coefficient of pea starch showed a significant effect (p < 0.05) on thickness, density, puncture force, water vapour permeability, and tensile strength. While tensile strength and Young modulus affected by the quadratic regression coefficient of glycerol and guar gum, respectively. The results were analysed using Pareto analysis of variance (ANOVA) and the developed predictive equations for each response variable presented reliable and satisfactory fit with high coefficient of determination (R2) values (≥ 0.96). The optimized conditions with the goal of maximizing mechanical properties and minimizing water vapour permeability were 2.5 g pea starch, 0.3 g guar gum and 25 % (w/w) glycerol based on the dry film matter in 100 ml of distilled water. Generally, changes in the concentrations of pea starch, guar gum and glycerol resulted in changes in the functional properties of film.

Development of Locust Bean Gum Nanoparticles for protein delivery

Dissertação de Mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2014

Inhalable antitubercular therapy mediated by locust bean gum microparticles

Tuberculosis remains a major global health problem and alternative therapeutic approaches are needed. Considering the high prevalence of lung tuberculosis (80% of cases), the pulmonary delivery of antitubercular drugs in a carrier system capable of reaching the alveoli, being recognised and phagocytosed by alveolar macrophages (mycobacterium hosts), would be a significant improvement to current oral drug regimens. Locust bean gum (LBG) is a polysaccharide composed of galactose and mannose residues, which may favour specific recognition by macrophages and potentiate phagocytosis. LBG microparticles produced by spray-drying are reported herein for the first time, incorporating either isoniazid or rifabutin, first-line antitubercular drugs (association efficiencies >82%). Microparticles have adequate theoretical properties for deep lung delivery (aerodynamic diameters between 1.15 and 1.67 μm). The cytotoxic evaluation in lung epithelial cells (A549 cells) and macrophages (THP-1 cells) revealed a toxic effect from rifabutin-loaded microparticles at the highest concentrations, but we may consider that these were very high comparing with in vivo conditions. LBG microparticles further evidenced strong ability to be captured by macrophages (percentage of phagocytosis >94%). Overall, the obtained data indicated the potential of the proposed system for tuberculosis therapy.

Mathematical-modelling simulation of red gum lerp psyllid Glycaspis brimblecombei population dynamics towards the strategy identification for biological control with its parasitoid Psyllaephagus bliteus.

2009

Preparation and characterization of chia seed protein isolate-chia seed gum complex coacervates

Chia seed protein isolate (CPI) and chia seed gum (CSG) were extracted and complex coacervation between these two was studied. The pH and the CPI-to-CSG ratio were optimized to obtain the highest yield of complex coacervates underpinned by zeta potential and turbidity values. CPI-CSG complex coacervates were found to form primarily due to electrostatic interaction and remained stable within a pH range of 2.1-2.9 at ambient temperature. The optimum pH and CPI-to-CSG ratio for complex coacervation was found to be 2.7 and 6:1, respectively. Spray dried complex coacervate particles possessed smoother surface morphology compared to the freeze dried ones. CPI-CSG complex coacervates demonstrated better thermal stability as compared to that of individual CPI and CSG. The crosslinking of these complex coacervates by transglutaminase further improved their thermal stability. Therefore, the crosslinked CPI-CSG complex coacervates will be able to better protect the oxygen and heat sensitive food and pharmaceutical ingredients.

Microencapsulation of flaxseed oil in flaxseed protein and flaxseed gum complex coacervates

Flaxseed oil, a rich source of omega-3 fatty acids, was microencapsulated in a novel matrix formed by complex coacervation between flaxseed protein isolate (FPI) and flaxseed gum (FG). This matrix was crosslinking with glutaraldehyde. Liquid microcapsules with three core (oil)-to-wall ratios (1:2, 1:3 and 1:4) were prepared and spray-dried or freeze-dried to produce powders. The microencapsulation efficiency, surface oil, morphology and oxidative stability of these microcapsules were determined. The spray-dried solid microcapsules had higher oil microencapsulation efficiency, lower surface oil content, smoother surface morphology and higher oxidation stability than the freeze-dried microcapsules. The highest microencapsulation efficiency obtained in spray-dried microcapsules was 87% with a surface oil of 2.78% at core-to-wall ratio 1:4 and oil load 20%. The oxidation stability obtained from spray-dried microcapsules at core-to-wall ratio of 1:4 was nearly double that of the unencapsulated flaxseed oil.

Microencapsulation of chia seed oil using chia seed protein isolate-chia seed gum complex coacervates

Chia seed oil (CSO) microcapsules were produced by using chia seed protein isolate (CPI)-chia seed gum (CSG) complex coacervates aiming to enhance the oxidative stability of CSO. The effect of wall material composition, core-to-wall ratio and method of drying on the microencapsulation efficiency (MEE) and oxidative stability (OS) was studied The microcapsules produced using CPI-CSG complex coacervates as wall material had higher MEE at equivalent payload, lower surface oil and higher OS compared to the microcapsules produced by using CSG and CPI individually. CSO microcapsules produced by using CSG as wall material had lowest MEE (67.3%) and oxidative stability index (OSI=6.6h), whereas CPI-CSG complex coacervate microcapsules had the highest MEE (93.9%) and OSI (12.3h). The MEE and OSI of microcapsules produced by using CPI as wall materials were in between those produced by using CSG and CPI-CSG complex coacervates as wall materials. The CSO microcapsules produced by using CPI-CSG complex coacervate as shell matrix at core-to-wall ratio of 1:2 had 6 times longer storage life compared to that of unencapsulated CSO. The peroxide value of CSO microcapsule produced using CPI-CSG complex coacervate as wall material was <10meq O2/kg oil during 30 days of storage.

Particle number and mass emission factors from combustion of wood samples collected from Queensland forest

Knowledge of particle emission characteristics associated with forest fires and in general, biomass burning, is becoming increasingly important due to the impact of these emissions on human health. Of particular importance is developing a better understanding of the size distribution of particles generated from forest combustion under different environmental conditions, as well as provision of emission factors for different particle size ranges. This study was aimed at quantifying particle emission factors from four types of wood found in South East Queensland forests: Spotted Gum (Corymbia citriodora), Red Gum (Eucalypt tereticornis), Blood Gum (Eucalypt intermedia), and Iron bark (Eucalypt decorticans); under controlled laboratory conditions. The experimental set up included a modified commercial stove connected to a dilution system designed for the conditions of the study. Measurements of particle number size distribution and concentration resulting from the burning of woods with a relatively homogenous moisture content (in the range of 15 to 26 %) and for different rates of burning were performed using a TSI Scanning Mobility Particle Sizer (SMPS) in the size range from 10 to 600 nm and a TSI Dust Trak for PM2.5. The results of the study in terms of the relationship between particle number size distribution and different condition of burning for different species show that particle number emission factors and PM2.5 mass emission factors depend on the type of wood and the burning rate; fast burning or slow burning. The average particle number emission factors for fast burning conditions are in the range of 3.3 x 1015 to 5.7 x 1015 particles/kg, and for PM2.5 are in the range of 139 to 217 mg/kg.