Controlled Release of 5-Fluorouracil from Alginate Beads Encapsulated in 3D Printed pH-Responsive Solid Dosage Forms

Three-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate particles were characterized for their physicochemical properties (thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction), their surface topography was visualized by scanning electron microscopy and the filaments’ mechanical properties were assessed by instrumented indentation testing and tensile testing. The optimized filament formulation was 3D printed and the structural integrity of the hollow tablet in increasing pH media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed tomography (μCT). In vitro release studies demonstrated controlled release of 5-FU from the alginate beads encapsulated within the hollow pH-sensitive tablet matrix at pH values corresponding to the colonic environment (pH 7.4). The present study highlights the potential of additive manufacturing in fabricating controlled-release dosage forms rendering them pertinent formulations for further in vivo evaluation.     

<Emphasis Type="Italic">In Vitro</Emphasis> Release Kinetics and Bioavailability of Gastroretentive Cinnarizine Hydrochloride Tablet

An oral sustained release dosage form of cinnarizine HCl (CNZ) based on gastric floating matrix tablets was studied. The release of CNZ from different floating matrix formulations containing four viscosity grades of hydroxypropyl methylcellulose, sodium alginate or polyethylene oxide, and gas-forming agent (sodium bicarbonate or calcium carbonate) was studied in simulated gastric fluid (pH 1.2). CNZ release data from the matrix tablets were analyzed kinetically using Higuchi, Peppas, Weibull, and Vergnaud models. From water uptake, matrix erosion studies, and drug release data, the overall release mechanism can be explained as a result of rapid hydration of polymer on the surface of the floating tablet and formation of a gel layer surrounding the matrix that controls water penetration into its center. On the basis of in vitro release data, batch HP1 (CNZ, HPMC-K100LV, SBC, LTS, and MgS) was subjected to bioavailability studies in rabbits and was compared with CNZ suspension. It was concluded that the greater bioavailability of HP1 was due to its longer retention in the gastric environment of the test animal. Batch no. HP1 of floating tablet in rabbits demonstrated that the floating tablet CNZ could be a 24-h sustained release formulation.     

Statistical Approach for Assessing the Influence of Calcium Silicate and HPMC on the Formulation of Novel Alfuzosin Hydrochloride Mucoadhesive-Floating Beads as Gastroretentive Drug Delivery Systems

Multiparticulate floating drug delivery systems have proven potential as controlled-release gastroretentive drug delivery systems that avoid the "all or none" gastric emptying nature of single-unit floating dosage forms. An objective of the presence investigation was to develop calcium silicate (CaSi)/calcium alginate (Ca-Alg)/hydroxypropyl methylcellulose (HPMC) mucoadhesive-floating beads that provide time- and site-specific drug release of alfuzosin hydrochloride (Alf). Beads were prepared by simultaneous internal and external gelation method utilizing 3(2) factorial design as an experimental design; with two main factors evaluated for their influence on the prepared beads; the concentration of CaSi as floating aid (X (1)) and the percentage of HPMC as viscosity enhancer and mucoadhesive polymer (X (2)), each of them was tested in three levels. Developed formulations were evaluated for yield, entrapment efficiency, particle size, surface topography, and buoyancy. Differential scanning calorimetry, Fourier transform infrared spectroscopy, in vitro drug release, as well as in vitro mucoadhesion using rat stomach mucosal membrane were also conducted. Percentage yield and entrapment efficiency ranged from 57.03% to 78.51% and from 49.78% to 83.26%, respectively. Statistical analysis using ANOVA proved that increasing the concentration of either CaSi or HPMC significantly increased the beads yield. Both CaSi and HPMC concentrations were found to significantly affect Alf release from the beads. Additionally, higher CaSi concentration significantly increased the beads diameter while HPMC concentration showed significant positive effect on the beads mucoadhesive properties. CaSi/Ca-Alg/HPMC beads represent simple floating-mucoadhesive gastroretentive system that could be useful in chronopharmacotherapy of benign prostatic hyperplasia.     

Design of innovated lipid-based floating beads loaded with an antispasmodic drug: in-vitro and in-vivo evaluation

Context: Drotaverine hydrochloride (DRT) is used to treat gastrointestinal spasms accompanied with diarrhoea. Hence, the drug suffers from brief residence in the highly moving intestine during diarrhoea which leads to poor bioavailability and frequent dosing.

Objective: This study aimed to extend DRT residence in the stomach.

Methods: Calcium alginate floating beads were prepared using sodium alginate, isopropylmyristate (oil), and Gelucire® 43/01 (lipid) adopting emulsion gelation technique. The beads were evaluated for their floating ability, DRT entrapment efficiency and in-vitro release. Gelucire® 43/01 /oil-based beads of the selected formula were coated using ethylcellulose and different plasticizers as polyethylene glycol 400 and triethyl citrate to retard the drug release. The coated beads were re-characterized. Finally, the best formulae were investigated for their in-vivo floating ability in dogs besides their delivery to the systemic circulation compared to drug powder in human volunteers.

Results: Incorporation of Gelucire® 43/01 to oil-based beads enhanced the in-vitro performance of the beads. Coated beads prepared using drug:sodium alginate ratio of 1:3 (w/w), 20% (w/v) isopropylmyristate, 20% (w/v) Gelucire® 43/01 showed promising in-vitro performance. The beads floated for 12?h in the dogs’ stomach and produced three-fold increase of the total amount of DRT absorbed within 24?h compared to that of DRT powder.

Conclusions: Gelucire® 43/01 /isopropylmyristate-based calcium alginate floating beads coated with ethylcellulose using either PEG 400 or TEC as plasticizers proved to be a successful dosage form in extending DRT release.     

Development and In Vivo Floating Behavior of Verapamil HCl Intragastric Floating Tablets

A novel gastro retentive controlled release drug delivery system of verapamil HCl was formulated in an effort to increase the gastric retention time of the dosage form and to control drug release. Hydroxypropylmethylcellulose (HPMC), carbopol, and xanthan gum were incorporated for gel-forming properties. Buoyancy was achieved by adding an effervescent mixture of sodium bicarbonate and anhydrous citric acid. In vitro drug release studies were performed, and drug release kinetics was evaluated using the linear regression method. The optimized intragastric floating tablet composed of 3:2 of HPMC K4M to xanthan gum exhibited 95.39% drug release in 24 h in vitro, while the buoyancy lag time was 36.2 s, and the intragastric floating tablet remained buoyant for >24 h. Zero-order and non-Fickian release transport was confirmed as the drug release mechanism from the optimized formulation (F7). X-ray studies showed that total buoyancy time was able to delay the gastric emptying of verapamil HCl intragastric floating tablet in mongrel dogs for more than 4 h. Optimized intragastric floating tablet showed no significant change in physical appearance, drug content, total buoyancy time, or in vitro dissolution pattern after storage at 40°C/75% relative humidity for 3 months.     

Development,Characterization and Permeability Assessment Based on Caco-2 Monolayers of Self-Microemulsifying Floating Tablets of Tetrahydrocurcumin

Novel self-microemulsifying floating tablets were developed to enhance the dissolution and oral absorption of the poorly water-soluble tetrahydrocurcumin (THC). Their physicochemical properties and THC permeability across Caco-2 cell monolayers were assessed. The self-microemulsifying liquid containing THC was adsorbed onto colloidal silicon dioxide, mixed with HPMC, gas-generating agents (sodium bicarbonate and tartaric acid), lactose and silicified-microcrystalline cellulose and transformed into tablets by direct compression. The use of different types/concentrations of HPMC and sodium bicarbonate in tablet formulations had different effects on the floating characteristics and in vitro THC release. The optimum tablet formulation (F2) provided a short floating lag time (∼23 s) together with a prolonged buoyancy (>12 h). About 72% of THC was released in 12 h with an emulsion droplet size in aqueous media of 33.9 ± 1.0 nm while that of a self-microemulsifying liquid was 29.9 ± 0.3 nm. The tablet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. The THC released from the self-microemulsifying liquid and tablet formulations provided an approximately three- to fivefold greater permeability across the Caco-2 cell monolayers than the unformulated THC and indicated an enhanced absorption of THC by the formulations. The self-microemulsifying floating tablet could provide a dosage form with the potential to improve the oral bioavailability of THC and other hydrophobic compounds.KEY WORDS: Caco-2 cells, controlled release, permeability, self-microemulsifying floating tablets, tetrahydrocurcumin     

Formulation and Evaluation of Swellable and Floating Gastroretentive Ciprofloxacin Hydrochloride Tablets

Drugs that have narrow absorption window in the gastrointestinal tract (GIT) will have poor absorption. For these drugs, gastroretentive drug delivery systems offer the advantage in prolonging the gastric emptying time. Swellable, floating, and sustained release tablets are developed by using a combination of hydrophilic polymer (hydroxypropyl methylcellulose), swelling agents (crospovidone, sodium starch glycolate, and croscarmelose sodium) and effervescent substance (sodium bicarbonate). Formulations are evaluated for percentage swelling, in vitro drug release, floating lag time, total duration of floating, and mean residence time (MRT) in the stomach. The drug release of optimized formulation follows the Higuchi kinetic model, and the mechanism is found to be non-Fickian/anomalous according to Krosmeyer–Peppas (n value is 0.68). The similarity factor (f ₂) is found to be 26.17 for the optimized formulation, which the release is not similar to that of marketed produced (CIFRAN OD®). In vivo nature of the tablet at different time intervals is observed in the radiographic pictures of the healthy volunteers and MRT in the stomach is found to be 320?±?48.99 min (n?=?6). A combination of HPMC K100M, crospovidone, and sodium carbonate shows the good swelling, drug release, and floating characters than the CIFRAN OD®.     

Enhanced Bioavailability of Atorvastatin Calcium from Stabilized Gastric Resident Formulation

Oral bioavailability of atorvastatin calcium (ATC) is very low (only 14%) due to instability and incomplete intestinal absorption and/or extensive gut wall extraction. When ATC is packed in the form of tablets, powders, etc., it gets destabilized as it is exposed to the oxidative environment, which is usually present during the production process, the storage of the substance, and the pharmaceutical formulation. Therefore, stabilized gastro-retentive floating tablets of ATC were prepared to enhance bioavailability. Water sorption and viscosity measurement studies are performed to get the best polymer matrix for gastro-retention. A 3² factorial design used to prepare optimized formulation of ATC. The selected excipients such as docusate sodium enhanced the stability and solubility of ATC in gastric media and tablet dosage form. The best formulation (F4) consisting of hypromellose, sodium bicarbonate, polyethylene oxide, docusate sodium, mannitol, crosscarmellose sodium, and magnesium stearate, gave floating lag time of 56 ± 4.16 s and good matrix integrity with in vitro dissolution of 98.2% in 12 h. After stability studies, no significant change was observed in stability, solubility, floating lag time, total floating duration, matrix integrity, and sustained drug release rates, as confirmed by DSC and powder X-ray diffraction studies. In vivo pharmacokinetic study performed in rabbits revealed enhanced bioavailability of F4 floating tablets, about 1.6 times compared with that of the conventional tablet (Storvas® 80 mg tablet). These results suggest that the gastric resident formulation is a promising approach for the oral delivery of ATC for improving bioavailability.Key words: atorvastatin calcium, bioavailibility, floating tablets, gastro-retention, stabilization     

Development and Optimization of Gastro-Retentive Controlled-Release Tablet of Calcium-Disodium Edentate and its In Vivo Gamma Scintigraphic Evaluation

Medical management of heavy metal toxicity, including radioactive ones, is a cause for concern because of their increased use in energy production, healthcare, and mining. Though chelating agents like EDTA and DTPA in parenteral form are available, no suitable oral formulation is there that can trap ingested heavy metal toxicants in the stomach itself, preventing their systemic absorption. The objective of the present study was to develop and optimize gastro-retentive controlled-release tablets of calcium-disodium edentate (Ca-Na₂EDTA). Gastro-retentive tablet of Ca-Na₂EDTA was prepared by direct compression method. Thirteen tablet formulations were designed using HPMC-K4M, sodium chloride, and carbopol-934 along with effervescing agents sodium bicarbonate and citric acid. Tablet swelling ability, in vitro buoyancy, and drug dissolution studies were conducted in 0.1 N HCl at 37 ± 0.5°C. Ca-Na₂EDTA was radiolabeled with technetium-99m for scintigraphy-based in vivo evaluation. Formula F8 (Ca-Na₂EDTA 200 mg, carbopol 100 mg, avicel 55 mg, citric acid 30 mg, NaHCO₃ 70 mg, NaCl 100 mg, and HPMC 95 mg) was found to be optimum in terms of excellent floating properties and sustained drug release. F8 fitted best for Korsmeyer–Peppas equation with an R² value of 0.993. Gamma scintigraphy in humans showed mean gastric retention period of 6 h. Stability studies carried out in accordance with ICH guidelines and analyzed at time intervals of 0, 1, 2, 4, and 6 months have indicated insignificant difference in tablet hardness, drug content, total floating duration, or matrix integrity of the optimized formulation. Gastro-retentive, controlled-release tablet of Ca-Na₂EDTA was successfully developed using effervescent technique as a potential oral antidote for neutralizing ingested heavy metal toxicity.KEY WORDS: calcium disodium EDTA, controlled-release tablet, gamma scintigraphy, heavy metal decorporation     

Investigation of factors influencing drug release using calcium alginate polymer

The effects of mixing, the sodium alginate concentration, and calcium chloride concentration on the release of sulphamethoxazole (model drug) impregnated in calcium alginate beads were investigated and evaluated. The release behaviour of the sulphamethoxazole from the calcium alginate beads was studied in a 0.1N HCl aqueous solution at 37v°C. The release rate of the sulphamethoxazole depends heavily on the type of mixers during the formation of the drug-alginate beads. The highest release rate was achieved when four-bladed rectangular agitator was used while the lowest release was achieved when magnetic stirrer was used. The amount of the released sulphamethoxazole varies slightly with the variation of the alginate concentration. The total release of sulphamethoxazole when 1% w/v solution of sodium alginate was used found to be 80% of the total drug content while 72% and 68% of the total drug content for 1.5% and 2% sodium alginate solutions. Three different calcium chloride concentrations were used (i.e., 5%, 10%, and 15% CaCl₂). The effect of the calcium chloride concentration on the release of the sulphamethoxazole is very pronounced.     

Evaluation of porous carrier-based floating orlistat microspheres for gastric delivery

The purpose of this research was to prepare floating microspheres consisting of (1) calcium silicate as porous carrier; (2) orlistat, an oral anti-obesity agent; and (3) Eudragit S as polymer, by solvent evaporation method and to evaluate their gastro-retentive and controlled-release properties. The effect of various formulation and process variables on the particle morphology, micromeritic properties, in vitro floating behavior, percentage drug entrapment, and in vitro drug release was studied. The gamma scintigraphy of the optimized formulation was performed in albino rabbits to monitor the transit of floating microspheres in the gastrointestinal tract. The orlistat-loaded optimized formulation was orally administered to albino rabbits, and blood samples collected were used to determine pharmacokinetic parameters of orlistat from floating microspheres. The microspheres were found to be regular in sphae and highly porous. Microsphere formulation CS4, containing 200 mg calcium silicate, showed the best floating ability (88%±4% buoyancy) in simulated gastric fluid as compared with other formulations. Release pattern of orlistat in simulated gastric fluid from all floating microspheres followed Higuchi matrix model and Peppas-Korsmeyer model. Prolonged gastric residence time of over 6 hours was achieved in all rabbits for calcium silicate-based floating microspheres of orlistat. The enhanced elimination half-life observed after pharmacokinetic investigations in the present study is due to the floating nature of the designed formulations.     

Artemisia arborescens L essential oil loaded beads: Preparation and characterization

The purpose of this work was to prepare sodium alginate beads as a device for the controlled release of essential oil for oral administration as an antiviral agent. Different formulations were prepared with sodium alginate as a natural polymer and calcium chloride or glutaraldehyde as a cross-linking agent. Loading capacities of between 86% and 100% were obtained in freshly prepared beads by changing exposure time to the cross-linking agent. Drying of the calcium alginate beads caused only a slight decrease in the loading efficiency. The surface morphology of the different bead formulations were studied using scanning electron microscopy (SEM). Stability studies over a 3-month period showed that glutaraldehyde reacted with some components ofArtemisia arborescens L essential oil, changing its composition. Calcium alginate beads showed an in vitro controlled release of the essential oil for the investigated 24 hours, while the use of glutaraldehyde as a cross-linking agent was found not appropriate because of the interactions with azulene derivatives and the low degree of matrix cross-linkage. Published: August 24, 2007     

Novel composite blend microbeads of sodium alginate coated with chitosan for controlled release of amoxicillin

Composite blend microbeads of sodium alginate (NaAlg) with sodium carboxymethyl cellulose (NaCMC) containing magnesium aluminum silicate (MAS) particles and enteric coated with chitosan have been prepared to achieve controlled release (CR) of amoxicillin in stomach environment. The composite beads have been characterized by X-ray diffraction (XRD) to study drug distribution, DSC for understanding thermal stability and Fourier transform infrared (FTIR) spectroscopy to investigate chemical interactions as well as to assess the structure of the drug-loaded formulations. Surface morphology of the beads was investigated by scanning electron microscopy (SEM). The size distribution of beads loaded with drug as studied by particle size analyzer was in the range of 745-889 μm. The beads exhibited quite widely varying encapsulation efficiencies from 52 to 92%. Equilibrium swelling of the beads measured in water and in vitro release of amoxicillin in pH 1.2 medium suggests that drug release depends on polymer blend composition, concentration of MAS and extent of enteric coating.     

海藻酸钠漂浮微囊的制备以及载药应用研究

目的:本文研究了一种海藻酸钠漂浮微囊的制备方法用以实现胃部持续给药。方法:采用微胶囊发生器制备海藻酸钠漂浮微囊,壁材为海藻酸钠,芯材为食用油的漂浮微囊,衡量不同的制备参数对微囊的理化特性影响;采用克拉霉素作为模型脂溶性药物,测量漂浮药物递送系统的控制释放性质、以及微囊载药特性和小鼠体内漂浮验证。结果:成功制备出了具有漂浮特性的海藻酸钠微囊,其中泵送速度对微囊性质的影响最大。制备出的微囊具有低细胞毒性,可以实现90%的药物包埋率。此外,微囊可以在小鼠的胃中保存超过6小时,具有良好的漂浮特性。结论:海藻酸钠漂浮微囊是一种有效的胃部药物递送系统,可明显延长药物在胃部的滞留时间。     

Development and Evaluation of oral multiple-unit and single-unit hydrophilic controlled-release systems

This study compared the release behavior of single-unit (tablets, capsules) and multiple-unit (minitablets in capsules) controlled-release systems of furosemide. The swelling and erosion behaviors of these systems, which contained the swellable hydrophilic polymers sodium alginate (high viscosity) and Carbopol 974P, were compared. Swelling and erosion experiments showed a high degree of swelling and limited erosion for the Carbopol preparations, whereas less swelling but greater erosion was observed for the sodium alginate preparations. The sodium alginate preparations were eroded in 6 hours, while Carbopol preparations exhibited limited erosion within this period of time. These results appear to be attributed to the physicochemical characteristics of the polymers used in this study. Polymer characteristics greatly influenced the release of furosemide (model drug) from the formulations prepared and tested. Sodium alginate had a less pronounced sustained release effect compared with Carbopol (ie, in 8 hours all 3 sodium alginate dosage forms displayed complete release of furosemide, while only 30% of the drug was released from Carbopol dosage forms). Finally, all 3 Carbopol dosage forms (single- and multiple-unit) displayed similar release behavior while sodium alginate dosage forms displayed a different and more distinctive behavior. Minitablets and tablets showed a greater sustained release effect compared with capsules. Evaluation of the release data indicates that the release mechanism for sodium alginate formulations may be attributed to erosion/dissolution, while for Carbopol it may be attributed mainly to polymer relaxation and diffusion of the drug from the polymer surface.     

Beaded matrices from cross-linked alginate for affinity and ion exchange chromatography of proteins

Summary To obtain a low cost, beaded chromatographic matrix, calcium alginate beads were cross-linked with epichlorohydrin, and calcium was removed by sodium citrate treatment. The cross-linking reaction for obtaining stable beads was optimized. For purification of haemoglobin by ion exchange, cross-linked calcium-free alginate beads have a q_max of 60 mg/ml and a K_d of 0.02 mg/ml gel, while for affinity polygalacturonase purification K_aff was 0.007 ml/g.     

Gastroretentive Matrix Tablets of Boswellia Oleogum Resin: Preparation,Optimization, <Emphasis Type="Italic">In Vitro</Emphasis> Evaluation,and Cytoprotective Effect on Indomethacin-Induced Gastric Ulcer in Rabbits

Currently available anti-ulcer drugs suffer from serious side effects which limited their uses and prompted the need to search for a safe and efficient new anti-ulcer agent. Boswellia gum resin (BR) emerged as a safe, efficient, natural, and economic potential cytoprotective agent. Thus, it is of medical importance to develop gastroretentive (GR) formulations of BR to enhance its bioavailability and anti-ulcer efficacy. Early attempts involved the use of organic solvents and non-applicability to large-scale production. In this study, different tablet formulations were prepared by simple direct compression combining floating and bioadhesion mechanisms employing hydroxypropyl methylcellulose (HPMC), sodium carboxymethyl cellulose (SCMC), pectin (PC), and/or carbopol (CP) as bioadhesive polymers and sodium bicarbonate (SB) as a gas former. The prepared tablets were subjected for assessment of swelling, floating, bioadhesion, and drug release in 0.1 N HCl. The optimized GR formulation was examined for its protective effect on the gastric ulcer induced by indomethacin in albino rabbits compared with lactose tablets. The obtained results disclosed that swelling, floating, bioadhesion, and drug release of the GR tablets of BR depend mainly on the nature of the matrix and the ratio of polymer combinations. Moreover, a combination of SCMC-CP in a ratio of 2:1 (SCP21) exhibited desirable floating, bioadhesion, swelling, and extended drug release. Also, a 6-h pretreatment with SCP21 tablets decreased the severity of inflammation and number of bleeding spots among ulcer-induced rabbits in comparison to those treated with lactose tablets.     

Wax-incorporated Emulsion Gel Beads of Calcium Pectinate for Intragastric Floating Drug Delivery

The purpose of this study was to prepare wax-incorporated pectin-based emulsion gel beads using a modified emulsion-gelation method. The waxes in pectin–olive oil mixtures containing a model drug, metronidazole, were hot-melted, homogenized and then extruded into calcium chloride solution. The beads formed were separated, washed with distilled water and dried for 12 h. The influence of various types and amounts of wax on floating and drug release behavior of emulsion gel beads of calcium pectinate was investigated. The drug-loaded gel beads were found to float on simulated gastric fluid if the sufficient amount of oil was used. Incorporation of wax into the emulsion gel beads affected the drug release. Water-soluble wax (i.e. polyethylene glycol) increased the drug release while other water-insoluble waxes (i.e. glyceryl monostearate, stearyl alcohol, carnauba wax, spermaceti wax and white wax) significantly retarded the drug release. Different waxes had a slight effect on the drug release. However, the increased amount of incorporated wax in the formulations significantly sustained the drug release while the beads remained floating. The results suggest that wax-incorporated emulsion gel beads could be used as a carrier for intragastric floating drug delivery.     

Development of Gelucire 43/01 Beads of Metformin Hydrochloride for Floating Delivery

The objective of this study was to prepare and characterize beads of Gelucire 43/01 for floating delivery of metformin hydrochloride (MH). The beads were evaluated for particle size, surface morphology, percent drug entrapment, percent yield, differential scanning calorimetry (DSC), in vitro floating ability, and in vitro drug release. Aging effect on storage was evaluated using hot stage microscopy (HSM), DSC, scanning electron microscopy, and in vitro floating ability. The formed beads were sufficiently hard and spherical in shape. Photomicrographs show that the surface was porous in nature. The average particle diameter of beads was found to be in the size range of 3.85 to 3.95 mm, and percent entrapment was 83.07% to 86.13%. The beads demonstrated favorable in vitro floating ability. The analysis of DSC thermograms revealed no physical interaction between the lipid and the drug in the prepared beads. Prepared formulations showed better controlled release behavior when compared with its conventional dosage form and comparable release profile with marketed sustained release product. HSM photomicrograph showed presence of some unmelted portion even at 43°C and completely melts on 51°C in aged sample. It was found that there was no significant effect on floating ability of aged beads since it remains floats up to 8 h study period. Thus, it is concluded that beads of Gelucire 43/01 could be serve as an effective carrier for highly water-soluble antihyperglycemic drugs like MH for the controlled delivery.     

Alginate modified nanostructured calcium carbonate with enhanced delivery efficiency for gene and drug delivery

To improve the performance of nanostructured calcium carbonate in gene delivery, a hydrophilic polysaccharide, alginate, was added to calcium carbonate co-precipitation systems to form alginate/CaCO(3)/DNA nanoparticles. The size and ζ-potential of the nanoparticles were measured by a zetasizer. Due to the existence of alginate chains which retarded the growth of calcium carbonate based co-precipitates, the alginate/CaCO(3)/DNA nanoparticles exhibited a decreased size and enhanced stability in the aqueous solution. To evaluate the gene and drug co-delivery ability, doxorubicin hydrochloride (DOX), a water-soluble anticancer drug, was loaded in the nanoparticles to form alginate/CaCO(3)/DNA/DOX nanoparticles. The in vitro gene transfections mediated by different nanoparticles in 293 T cells and HeLa cells were carried out, using pGL3-Luc as a reporter plasmid. With an appropriate amount of alginate, the gene transfection efficiency of alginate modified nanoparticles could be significantly enhanced as compared with the nanoparticles without alginate modification for the gene delivery systems, as well as the gene and drug co-delivery systems. The study on in vitro cell inhibition effects showed that the cell viability decreased with increasing DOX amount loaded in alginate/CaCO(3)/DNA/DOX nanoparticles. The alginate modification is a useful strategy to improve the calcium carbonate co-precipitation technique for the preparation of gene and drug delivery systems, and the nanoparticles prepared in this study have promising applications in gene and drug delivery.