case-II Transport Research Articles

Swelling and drug release behavior of metformin HCl-loaded tamarind seed polysaccharide-alginate beads

The paper describes the preparation, characterization, in vitro swelling and in vitro drug release of metformin HCl-loaded tamarind seed polysaccharide (TSP)-alginate beads were prepared by ionotropic-gelation technique and using CaCl2 as cross-linker. The prepared beads exhibited 32.73±1.41% of drug loading (%), 94.86±3.92% of drug encapsulation efficiency (%), and 1.24±0.07mm of average bead size. The bead surface morphology was analyzed by SEM. The drug–polymer interaction in the bead matrix was analyzed by FTIR analyses. These metformin HCl-loaded ionotropically gelled TSP-alginate beads demonstrated sustained in vitro drug release profile over 10h. These in vitro drug release exhibited pH-dependent drug release behavior. The in vitro drug release from these metformin HCl-loaded beads followed controlled-release (zero-order) pattern with super case-II transport mechanism. The swelling and degradation of these metformin HCl-loaded polymeric beads were found to be influenced by the pH of test mediums.

Preparation of uniform starch microcapsules by premix membrane emulsion for controlled release of avermectin

In recent years, starch microparticles have gained interest in many fields. However, low production, uncontrollable size, and varying size distribution hinder their practical application. Here, we adopt a premix membrane emulsification (PME) method to prepare starch microcapsules at high production rates. The process conditions were optimized to fabricate uniform microcapsules with controllable sizes and narrow size distribution (PDI<0.1). Through encapsulating avermectin (Av), a kind of water-insoluble pesticide, into the shell of the microcapsules in situ during the process, we developed a pesticide delivery system that enabled a controlled and consistent release of Av over a period of 2 weeks. Kinetic analysis indicated that the mechanisms of Av release involved non-Fickian and Case-II transport. The diameters (0.70–4.8μm) of the microcapsules and Av contents (16–47%) were adjusted to achieve suitable release profiles. The results will lay the foundation for further field experiments.

Characterisation of a novel, multifunctional, co-processed excipient and its effect on release profile of paracetamol from tablets prepared by direct compression

ObjectiveTo characterise a novel multifunctional pharmaceutical excipient and investigate its effect on paracetamol release from tablets prepared by direct compression. MethodsThe excipient was prepared by co-processing gelatinized maize starch with sodium carboxymethyl cellulose and microcrystalline cellulose in a ratio of 2:1:1, dried and pulverized into powder. The excipient formulated was characterized using Fourier transform infrared spectroscopy and differential scanning calorimetry. The excipient was used to prepare batches of tablets by direct compression with drug-excipient ratios of 1:1, 1:2, 1:3 and 1:4. Parameters evaluated on tablets include crushing strength, friability and in vitro dissolution studies. ResultsDifferential scanning calorimetry analysis revealed a crystalline excipient while Fourier transform infrared spectroscopy showed no interaction between the excipient and paracetamol. Tablets from all the batches gave average crushing strength values between 3.47 and 4.88 kp. The 1:1 and 1:2 tablet batches were comparable to each other while 1:3 and 1:4 were also comparable to one another in their dissolution profiles. The dissolution parameters of the 1:4 batch was faster with – m∞ (90.5%), t50% (3.5 min), t70% (11.6 min) while that of ratio 1:1 was the least with – m∞ (48.6%), m5min (23.8%). Their release kinetics followed a Korsmeyer–Peppas model with a super case-II transport mechanism. ConclusionsThe drug-excipient ratios of 1:3 and 1:4 gave pharmaceutically acceptable tablets that met the British Pharmacopoeia specifications. The t50% value of the 1:4 batch of tablets may find its usefulness in formulating drugs for which a fast onset of action is desired.

Formulation and In vitro Evaluation of Modified Release Oral Hydrogel Driven Drug Delivery Systems of Diethylcarbamazine Citrate

Objective: Hydrogels are three dimensional polymer matrices that are capable of imbibing large quantity of water, and biological fluids and used in the modifying release of the drugs. The present work was aimed to study oral hydrogel driven drug delivery systems of Diethylcarbamazine Citrate as a model drug. Methodology: The Hydrogels were composed of Poly acrylamide, Hydroxyethyl methacrylate using ionotropic gelation method using starch. Results: Thermographs showed no incompatibility between the drug and the polymers. Scanning Electron photomicrographs showed a rough contour surface. Drug release studied by High Pressure Liquid Chromatography using acetonitrile/0•01M phosphate buffer pH 6•8 at 210 nm showed that Formulation 9 released 98.67% of the dose in 16 h as compared to the marketed formulation which released 98.66% up to 6 h. The release followed first order kinetics and non-fickian diffusion by super case-II transport mechanism. Accelerated stability studies performed as per ICH guidelines at 40° ± 2° and 75 ± 5% RH and at ambient conditions of 25° ± 2° and 60 ± 5% RH showed that the hydrogel was stabile. Conclusion: It is concluded that hydrogel can be recommended as modified release dosage forms for industrial applications.

Alginate-okra gum blend beads of diclofenac sodium from aqueous template using ZnSO4 as a cross-linker

Zinc (Zn2+)-ion induced diclofenac sodium (DS)-loaded alginate-okra (Hibiscus esculentus) gum (OG) blend beads was successfully formulated through Zn2+-ion induced ionic-gelation cross-linking method in a complete aqueous environment. Effects of polymer-blend ratio and cross-linker concentration on drug encapsulation efficiency (DEE) and cumulative drug release at 8h (R8h) were optimized by 32-factorial design. The optimized formulation of Zn2+-ion induced DS-loaded alginate-OG beads demonstrated 89.27±3.58% of DEE and 43.73±2.83% of R8h. The bead sizes were within 1.10±0.07 to 1.38±0.14mm. The bead surface morphology was analyzed by SEM. The drug–polymer interaction in the optimized bead matrix was analyzed by FTIR and P-XRD. These beads exhibited sustained in vitro drug release over a prolonged period of 8h and followed controlled-release (zero-order) pattern with super case-II transport mechanism. The swelling and degradation of the optimized beads was influenced by the pH of test mediums, which might be suitable for intestinal drug delivery.

Some Physical Properties of &lt;i&gt;Vernonia amygdalina&lt;/i&gt; and &lt;i&gt;Garcinia kola&lt;/i&gt; Microspheres Prepared with High Molecular Weight Polyethylene Glycols

The effect of polymer concentrations on some of the physicochemical properties of Vernonia amygdalina (Linn) and Garcinia kola (Heckel) extracts loaded microspheres was evaluated. Microspheres of the aqueous extracts was prepared by emulsion solvent evaporation using polyethylene glycol (PEG) mixtures of molecular weight 4000 and 6000 at different ratios of 1:0, 0:1, 1:1, 1:2 and 2:1 while the amounts of the extracts incorporated was constant for all ratios. The microspheres were evaluated for their particles sizes, yield, flavonoid content, loading efficiency, moisture loss and flow properties. In-vitro release studies were carried out by monitoring flavonoid release rate from the microspheres. The microspheres were spherical and uniformly shaped and exhibited good flow characteristics. Their size range, yield, loading efficiency, moisture loss and flavonoid content were 76 - 83 im, 49 - 76 %, 47 - 82 %, 2.18 - 4.60 % and 17.10 - 23.80 mg%, respectively for V. amygdalina and 144 - 160 im, 50 - 68 %, 51 - 68 %, 3.00 - 4.41 % and 20.00 - 28.70 mg%, respectively for G. kola . Flavonoids release from the microsphere was up to 90 % within 1 h and it followed a matrix release kinetic model with a super case-II transport mechanism. The concentrations of the polymers affected the yield, loading efficiency, moisture loss and the extent of flavonoid release of the microspheres but had no effect on their particle sizes and flavonoid content. These results may find useful application in the delivery of V. amygdalina and G. kola extracts since the combination of PEG of different molecular weights resulted in microspheres with good physicochemical and release properties. © JASEM

Modelling the transport of toluene liquid in protective polymer gloves using a fluorescent dye-tracing technique

The absence of adequate information about the phase change of liquid solvents within polymer-glove walls hinders the complete characterisation of the mass transfer of toluene liquid through the polymer membranes using the data obtained from ASTM F739 method for toluene liquid permeation testing. Therefore, an alternative fluorescent dye-tracing technique is used to account for the transport processes of toluene liquid through polymer gloves. The results of dye penetration experiments show that the displacement of liquid-phase toluene is proportional to the square root of immersion time, indicating that the transport behaviour of liquid-phase toluene is dominated by Fickian diffusion. Furthermore, a linear relationship between the mass sorption of toluene vapour and the sampling time is established, which suggests that the diffusion process in the vapour-phase toluene is governed by Case-II transport. Based on the combined analysis of the results obtained from permeation tests, immersion tests, fluorescent dye-tracer tests, and the pertinent calculations of thermodynamic properties, an evidence-based mechanism for the mass transfer of toluene liquid through the polymer-glove walls is proposed in terms of time-series processes. The model comprises three regimes: a liquid phase, a combined liquid–vapour phase, and a vapour phase of toluene that exist in series within the membrane.

Formulation and In-Vitro Evaluation of Liposomal Drug Delivery System of Cabazitaxel

Formulation and In-Vitro Evaluation of Liposomal Drug Delivery System of Cabazitaxel Cabazitaxel is a semi-synthetic derivative of a natural taxoid and is used for the treatment of advanced prostate cancer. In the present study Cabazitaxel liposomes were prepared by thin film hydration technique using lecithin, cholesterol, and Tween 80. Six formulations of liposomes were evaluated for physico chemical properties and in vitro drug release. The compatibility of drug with other ingredients was checked by FTIR studies. The prepared liposomes were characterized for surface morphology by SEM analysis, Percentage drug entrapment efficiency, Particle size, and Zeta potential analysis. The in-vitro drug release for optimized formulation F2 followed zero-order release kinetics. F2 was formulated using 270 mg lecithin and 30 mg cholesterol and 0.5 ml of Tween 80 with an objective to achieve a linear release profile for 24 hr. There was no initial burst release, with 5.68% of drug released during the first hour and release was extended up to 24 hrs. Study of drug release kinetics was performed by application of in-vitro drug release data to various kinetic equations like zero-order; first order, Higuchi and Korsmeyer-Peppas and from ‘n’ value (1.515) it was concluded that the drug release followed zero order kinetics with super case-II transport which indicates both erosion and diffusion as the release mechanisms. Stability studies at different temperatures were conducted and maximum drug retention was found at refrigerated temperature 4oC.

Novel alginate hydrogel core–shell systems for combination delivery of ranitidine HCl and aceclofenac

A novel hydrogel system was successfully developed based on core–shell approach for the delivery of ranitidine HCl and aceclofenac. Aceclofenac-loaded alginate microspheres coated with eudragit L-100 was used as core material and that of freeze–thaw cross-linked chitosan–PVA gels containing ranitidine HCl served as the shell-forming material. The alginate microspheres coated with eudragit L-100 showed drug encapsulation efficiency of 56.06±1.12 to 68.03±2.16% and had average particle sizes of 551.29±25.92 to 677.18±27.05μm. The viscosity of chitosan–PVA gels ranged between 505.74±1.04 and 582.41±2.09 cps. The formulations were characterized by FTIR, SEM and polarized microscopy analyses. The release of ranitidine HCl was comparatively higher in acidic medium (pH 1.2) than in alkaline medium (pH 7.4). The release of aceclofenac became slower in alkaline medium (pH 7.4) and continued up to 3.5h. Super case-II transport mechanism was assumed for the release of ranitidine HCl in both media; whereas non-Fickian (anomalous) diffusion mechanism predominated in the release of aceclofenc. Thus, hydrogel-based core–shell formulations were found suitable for simultaneous delivery of aceclofenac and ranitidine HCl which could minimize the chances of excessive gastric acid secretion through suitable ranitidine HCl release in gastric region.

Okra (Hibiscus esculentus) gum-alginate blend mucoadhesive beads for controlled glibenclamide release

The utility of isolated okra (Hibiscus esculentus) gum (OG) was evaluated as a potential sustained drug release polymer-blends with sodium alginate in the development of controlled glibenclamide release ionically-gelled beads for oral use. OG was isolated from okra fruits and its solubility, pH, viscosity and moisture content were studied. Glibenclamide-loaded OG-alginate blend beads were prepared using CaCl2 as cross-linking agent through ionic-gelation technique. These ionically gelled beads showed drug entrapment efficiency of 64.19±2.02 to 91.86±3.24%. The bead sizes were within 1.12±0.11 to 1.28±0.15mm. These glibenclamide-loaded OG-alginate blend beads exhibited sustained in vitro drug release over a prolonged period of 8h. The in vitro drug release from these OG-alginate beads were followed controlled-release (zero-order) pattern with super case-II transport mechanism. The beads were also characterized by SEM and FTIR. The swelling and degradation of these beads was influenced by the pH of the test medium. These beads also exhibited good mucoadhesivity with goat intestinal mucosa.

Mucoadhesive beads of gellan gum/pectin intended to controlled delivery of drugs

Gellan gum/pectin beads were prepared by ionotropic gelation, using Al3+ as crosslinker. High yield (92.76%) and entrapment efficiency (52.22–88.78%) were reached. Beads exhibited high circularity (0.730–0.849) and size between 728.95 and 924.56μm. Particle size and circularity was increased by raising polymer and crosslinker concentrations. Polymers ratio did not influence beads properties. The materials stability and the absence of drug–polymers interactions were evidenced by thermal analysis and FTIR. The high beads mucoadhesiveness was evidenced by in vitro and ex vivo tests. The erosion of beads was greater in acid media while swelling was more pronounced in pH 7.4. Drug release was dependent on pH in which samples 11H1-3, 11H1-5 and 41H1-3 released only 34%, 20% and 22% of ketoprofen in pH 1.2, while in pH 7.4 the drug release was sustained up to 360min. Korsmeyer–Peppas model demonstrated that drug release occurred according to super case-II transport.

Locust bean gum in the development of sustained release mucoadhesive macromolecules of aceclofenac

The study shows the development and optimization of locust bean gum (LBG)–alginate mucoadhesive macromolecules containing aceclofenac through ionotropic-gelation using 32 factorial design. The effect of amount of LBG and sodium alginate on drug entrapment efficiency (%DEE), % mucoadhesion at 8h (M8) and % in vitro drug release at 10h (%Q10h) were optimized. The percentage yield, average size and DEE of macromolecules were found within the range of 93.19 to 96.65%, 1.328±0.11 to 1.428±0.13μm, and 56.37 to 68.54%, respectively. The macromolecules were also characterized by SEM, FTIR and DSC. The in vitro drug release from these macromolecules (84.95±2.02 to 95.33±1.56% at 10h) exhibited sustained release (first-order) pattern with super case-II transport mechanism. The swelling and mucoadhesivity of these macromolecules were affected by pH of the medium. The design established the role of derived polynomial equations and plots in predicting the values of dependent variables for the preparation and optimization.

Development of pectinate-ispagula mucilage mucoadhesive beads of metformin HCl by central composite design

Ionotropically-gelled mucoadhesive beads of metformin HCl composed of low methoxy (LM) pectin-ispaghula husk mucilage (IHM) polymer-blend was developed and optimized using central composite design (spherical type, single center point, and α=1.414). Effects of LM pectin and IHM amounts on drug encapsulation efficiency (DEE) and cumulative drug release at 10h (R10h) were analysed using response surface methodology. The optimized beads containing metformin HCl (F-O) showed DEE of 86.98±3.26% and R10h of 47.20±1.28%. All these beads exhibited suitable controlled in vitro sustained drug release pattern with super case-II transport mechanism over 10h. These beads were also characterized by SEM and FTIR. The optimized beads also exhibited pH-dependent swelling, good mucoadhesivity with goat intestinal mucosa and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration, which could possibly be lucrative in terms of prolonged systemic absorption of metformin HCl maintaining tight blood glucose level and advanced patient compliance.

Trigonella foenum-graecum L. seed mucilage-gellan mucoadhesive beads for controlled release of metformin HCl

Fenugreek (Trigonella foenum-graecum L.) seed mucilage (FSM)-gellan gum (GG) mucoadhesive beads containing metformin HCl for oral use were developed through ionotropic-gelation technique. Effects of GG to FSM ratio and cross-linker (CaCl2) concentration on the drug encapsulation efficiency (DEE, %), and cumulative drug release after 10h (R10h, %) of ionotropically-gelled FSM-GG mucoadhesive beads containing metformin HCl were optimized by 32 factorial design. The optimized mucoadhesive beads showed DEE of 92.53±3.85% and R10h of 55.28±1.58% and mean diameter of 1.62±0.22mm. The in vitro metformin HCl release from these ionotropically-gelled FSM-GG beads was prolonged over 10h and followed zero-order model with super case-II transport mechanism. The optimized mucoadhesive beads also exhibited pH-dependent swelling, good mucoadhesivity with biological mucosal membrane and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration.

Ispaghula mucilage-gellan mucoadhesive beads of metformin HCl: Development by response surface methodology

Response surface methodology based on 32 factorial design was used to develop ispaghula (Plantago ovata F.) husk mucilage (IHM)-gellan gum (GG) mucoadhesive beads containing metformin HCl through Ca2+-ion cross-linked ionotropic-gelation technique for the use in oral drug delivery. GG to IHM ratio and cross-linker (CaCl2) concentration were investigated as independent variables. Drug encapsulation efficiency (DEE, %) and cumulative drug release after 10h (R10h, %) were analyzed as dependent variables. The optimized mucoadhesive beads (F-O) showed DEE of 94.24±4.18%, R10h of 59.13±2.27%. These beads were also characterized by SEM and FTIR analyses. The in vitro drug release from these beads showed controlled-release (zero-order) pattern with super case-II transport mechanism over 10h. The optimized beads showed pH-dependent swelling and good mucoadhesivity with the goat intestinal mucosa. The optimized IHM-GG mucoadhesive beads containing metformin HCl exhibited significant antidiabetic effect in alloxan-induced diabetic rats over 10h.

Artocarpus heterophyllus L. seed starch-blended gellan gum mucoadhesive beads of metformin HCl

Jackfruit (Artocarpus heterophyllus Lam., family: Moraceae) seed starch (JFSS)–gellan gum (GG) mucoadhesive beads containing metformin HCl were developed through ionotropic gelation technique. The effect of GG to JFSS ratio and CaCl2 concentration on the drug encapsulation efficiency (DEE, %) and cumulative drug release at 10h (R10h, %) was optimized and analyzed using response surface methodology based on 32 factorial design. The optimized JFSS–GG beads containing metformin HCl showed DEE of 92.67±4.46%, R10h of 61.30±2.37%, and mean diameter of 1.67±0.27mm. The optimized beads showed pH-dependent swelling and mucoadhesivity with the goat intestinal mucosa. The in vitro drug release from all these JFSS–GG beads containing metformin HCl was followed zero-order pattern (R2=0.9907–0.9975) with super case-II transport mechanism over a period of 10h. The beads were also characterized by SEM and FTIR. The optimized JFSS–GG beads containing metformin HCl exhibited significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration.

Controlled release of diclofenac sodium through acrylamide grafted hydroxyethyl cellulose and sodium alginate

To reinforce the hydroxyethyl cellulose for using it in biomedical and pharmaceutical applications as a drug delivery systems, the grafting of acrylamide onto hydroxyethyl cellulose (AAm-g-HEC) was achieved by Ce(IV) induced free radical polymerization. The AAm-g-HEC was then blended with sodium alginate (NaAlg) to prepare pH-sensitive interpenetrating network (IPN) microspheres (MPs) by emulsion-crosslinking method using glutaraldehyde (GA) as a crosslinking agent. The produced MPs are almost spherical in nature with smooth surfaces. Diclofenac sodium (DS), an anti-inflammatory drug, was successfully encapsulated into the MPs. The % encapsulation efficiency was found to vary between 54 and 67. The MPs were characterized by DSC, SEM and FTIR spectroscopy. In vitro release studies were carried out in simulated gastric fluid of pH 1.2 for 2h followed by simulated intestinal fluid of pH 7.4 at 37°C. The release data have been fitted to an empirical equation to investigate the diffusional exponent (n), which indicated that the release mechanism shifted from anomalous to the super Case-II transport.

Glutaraldehyde Cross linked Sodium Alginate / Chitosan pH Sensitive Microspheres for Controlled Release of Ibuprofen , Preparation and characterization

polymers of sodium alginate and chitosan (NaAlg/Cs) based pH-Sensitive interpenetrating network (IPN) microspheres (MPs) were prepared by emulsion- crosslinking technique using glutaraldehyde (GA) as a crosslinking agent. Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID) was successfully encapsulated The biodegradable into the MPs by varying the ratio of % Cs, amount of GA and % drug loading. MPs with average particle sizes in the range of 293-372 µm were obtained. MPs were characterized by Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and Differential scanning calorimetry (DSC). In Vitro release studies were carried out in simulated gastric fluid of pH 1.2 for 2 h followed by simulated intestinal fluid of pH 7.4 at 37oC. In conclusion, the present study indicates that Ibuprofen was successfully encapsulated into the hydrophilic carbohydrate polymers blend MPs composed of NaAlg and Cs. The encapsulation efficiency up to 84% was obtained. The release of drug from the MPs was dependent upon the pH of medium, % Cs ratio, extent of GA and amount of drug loading. The n values ranged between 0.89 and 1.17, indicating that the drug release from the MPs shifted from anomalous to the super Case-II transport. FTIR confirmed the formations of IPN MPs. DSC have confirmed the amorphous dispersion of the drug in the polymer matrix.

Topical gels of lidocaine HCl using cashew gum and Carbopol 940: Preparation and in vitro skin permeation

The present study was attempted to prepare novel topical gels of 4% lidocaine HCl using cashew gum and Carbopol 940. The prepared gels were evaluated for pH, viscosity, and in vitro skin permeation through excised porcine skin. The pH of these topical gels was found within the range of 5.98–6.06; whereas, the viscosity was found 4.58×106 to 4.88×106cps. The in vitro skin permeation from these gels showed permeation flux range, 851.34±9.16 to 1568.15±14.03μg/cm2/h. The highest permeation flux (1568.15±14.03μg/cm2/h) was observed, when 0.01% menthol was added, which was higher than that of the marketed 4% lidicaine HCl topical gel (1355.41±10.92μg/cm2/h). These topical gels found best-fit with Korsmeyer–Peppas model and almost the super case-II transport mechanism. The stability study revealed that these gels were physically stable without occurrence of syneresis.

Development of calcium pectinate-tamarind seed polysaccharide mucoadhesive beads containing metformin HCl

Novel mucoadhesive beads containing metformin HCl made of low methoxy (LM) pectin-tamarind seed polysaccharide (TSP) polymer-blend was developed through ionotropic-gelation technique and optimized using 32 factorial design. Effects of LM pectin and TSP amounts on drug encapsulation efficiency (DEE), and cumulative drug release at 10h (R10h) were analyzed using response surface methodology. The optimized calcium pectinate-TSP beads containing metformin HCl showed DEE of 95.12±4.26%, R10h of 46.53±3.28%, and mean diameter of 1.93±0.26mm. The in vitro drug release from these beads was followed controlled-release (zero-order) pattern with super case-II transport mechanism. These beads were also characterized by SEM and FTIR. The optimized beads also exhibited pH-dependent swelling, good mucoadhesivity with goat intestinal mucosa and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration.