Immediate-Release Formulations Produced via Twin-Screw Melt Granulation: Systematic Evaluation of the Addition of Disintegrants.

The current study evaluated the effect of location and amount of various superdisintegrants on the properties of tablets made by twin-screw melt granulation (TSMG). Sodium-croscarmellose (CCS), crospovidone (CPV), and sodium starch glycolate (SSG) were used in various proportions intra- and extra-granular. Tabletability, compactibility, compressibility as well as friability, disintegration, and dissolution performance were assessed. The extra-granular addition resulted in the fasted disintegration and dissolution. CPV performed superior to CCS and SSG. Even if the solid fraction (SF) of the granules was lower for CPV, only a minor decrease in tabletability was observed, due to the high plastic deformation of the melt granules. The intra-granular addition of CPV resulted in a more prolonged dissolution profile, which could be correlated to a loss in porosity during tableting. The 100% intra-granular addition of the CPV resulted in a distinct decrease of the disintegration efficiency, whereas the performance of SSG was unaffected by the granulation process. CCS was not suitable to be used for the production of an immediate-release formulation, when added in total proportion into the granulation phase, but its efficiency was less impaired compared to CPV. Shortest disintegration (78 s) and dissolution (Q80: 4.2 min) was achieved with CPV extra-granular. Using CPV and CCS intra-granular resulted in increased disintegration time and Q80. However, at a higher level of appx. 500 s and appx. 15 min, only SSG showed a process and location independent disintegration and dissolution performance.

Effect of gamma sterilization on the properties of microneedle array transdermal patch system.

Soluble microneedles (MNs) of four different hydrophilic polymers namely sodium carboxymethyl cellulose (CMC), polyvinylpyrrolidone (PVP) K30, PVP K90 and sodium hyaluronate (HU) were fabricated by mold casting technique. When exposed to gamma radiation, a dose of 25 kilogray (kGy) was found to render the microneedle (MN) sterile. However, CMC was found to form MNs with poor mechanical properties, whereas PVP K30 MNs were drastically deformed upon exposure to applied dose as observed in bright field microscopy. Scanning electron microscopy (SEM) revealed that morphology of PVP K90 and HU MNs were not significantly affected at the applied dose. The appearances of characteristic peaks of irradiated MNs of PVP K90 and HU in Fourier-transform infrared spectra suggested structural integrity of the polymers on irradiation. Differential scanning calorimetry (DSC) indicated gamma irradiation failed to alter the glass transition temperature and thus mechanical properties of PVP K90 MNs. However, DSC and Powder X-ray Diffraction (PXRD) conclusively indicated that the degree in crystallinity of HU was substantially reduced on irradiation. In vitro dissolution profiles of sterile PVP K90 and HU MNs were similar to un-irradiated MNs with a similarity factor (f2) of 64 and 54, respectively. In vivo dissolution studies in human subjects indicated that sterile MNs of PVP K90 and HU exhibited dissolution of 78.45 ± 1.09 and 78.57 ± 0.70%, respectively, after 20 min. The studies suggested that PVP K90 and HU could be suitable polymers to fabricate soluble MNs as the structural, morphological, microstructural and dissolution properties remained unaltered post γ sterilization.

Graphene quantum dot cross-linked carboxymethyl cellulose nanocomposite hydrogel for pH-sensitive oral anticancer drug delivery with potential bioimaging properties.

Herein, graphene quantum dots (GQDs) were introduced as a novel and safe crosslinker for carboxymethyl cellulose to make biodegradable and biocompatible hydrogels. The casting was used as a simple method for the preparation of the CMC/GQDs films. Effects of the GQDs percentage on the physicochemical properties of the films were studied, and several characterizations were performed including Fourier transform infrared spectroscopy, UV-vis spectroscopy, scanning electron microscopy, gas permeability, and mechanical testing analysis. The CMC/GQDs showed a pH-sensitive swelling and degradation with improved tensile strength. Fluorescent properties were also studied to evaluate the potential of the prepared CMC/GQDs nanocomposite for fluorescent bioimaging applications. Drug delivery property of the CMC-GQDs were studied using doxorubicin (DOX) as a model anticancer drug. Cytotoxicity studies were carried out using human colon adenocarcinoma HT29 cells. The prepared CMC/GQDs exhibited biocompatibility and pH-sensitive drug delivery behavior which proposed the prepared nanocomposite hydrogel has the potential to be used as a pH-triggered site-specific drug delivery system.

Formulation and Artificial Sebum Effects on the Percutaneous Absorption of Zinc Pyrithione through Excised Human Skin.

BACKGROUND: Zinc pyrithione (ZnPT) is deposited on the skin as a fine particulate and must reach microorganisms localized in the stratum corneum and hair follicles in molecular form to exert its broad-spectrum antimicrobial/antifungal activity. Dissolution of ZnPT particles followed by molecular speciation results in the organic portion, i.e. pyrithione, being more susceptible to skin penetration than the inorganic component, i.e. zinc, or the chelate itself, i.e. ZnPT. OBJECTIVES: To further test the hypothesis that ZnPT skin penetration is rate-limited by dissolution and molecular speciation, the effect of different formulations and artificial sebum on the in vitro percutaneous absorption of radiolabel associated with Zn[14C]PT was investigated. METHOD: In vitro penetration of [14C]PT into and through excised human skin was measured following application of Zn[14C]PT prepared as suspensions in distinct vehicles including water-based carboxymethylcellulose (CMC), diluted body wash comprised of surfactants, and castor oil, in the presence and absence of artificial sebum. RESULTS: The steady-state flux and cumulative absorption of Zn[14C]PT increased 4- to 5-fold when deposited from a body wash or castor oil compared to a water-based CMC suspension. Tritiated water flux measured before and after treatment showed that neither the surfactant vehicle nor castor oil significantly altered barrier function versus water alone. An artificial sebum layer on the skin potentiated Zn[14C]PT and 3H2O absorption when dosed from both aqueous formulations, but not from castor oil. CONCLUSION: These data are consistent with the hypothesis that ZnPT percutaneous absorption, as measured by [14C]PT kinetics, is controlled by particle dissolution and molecular speciation.

Facile preparation of a Ca(ii) carboxymethyl cellulose complex with enhanced calcium bioavailability for treatment of osteoporosis.

At present, though calcium (Ca) reagents with high calcium contents are widely synthesized, their wide application is limited due to their low absorption rates and poor bioavailability. Here we use a carboxymethyl cellulose (CMC) derivative with high water solubility and biocompatibility as a ligand to bind Ca2+. The resulting CaCMC complex exhibits remarkable solubility and absorbability under both basic and acidic conditions as well as in stomach mimicking and the gastrointestinal tract. Importantly, this Ca reagent shows high in vivo calcium bioavailability. Data from osteoporosis mouse models show that the CaCMC complex is superior to calcium carbonate in the treatment of osteoporosis. Therefore, the resulting CaCMC complex is used as a new, highly effective and desirable Ca supplement for daily life and clinical applications.

Systematic Evaluation of a Diclofenac-Loaded Carboxymethyl Cellulose-Based Wound Dressing and Its Release Performance with Changing pH and Temperature.

Development of drug-loaded wound dressings is often performed without systematic consideration of the changing wound environment that can influence such materials' performance. Among the crucial changes are the wound pH and temperature, which have an immense effect on the drug release. Detailed release studies based on the consideration of these changing properties provide an important aspect of the in vitro performance testing of novel wound dressing materials. A sodium carboxymethyl cellulose-based wound dressing, with the incorporated non-steroidal anti-inflammatory drug diclofenac, was developed and characterised in regard to its physico-chemical, structural and morphological properties. Further, the influence of pH and temperature were studied on the drug release. Finally, the biocompatibility of the wound dressing towards human skin cells was tested. Incorporation of diclofenac did not alter important properties (water retention value, air permeability) of the host material. Changes in the pH and temperature were shown to influence the release performance and have to be accounted for in the evaluation of such dressings. Furthermore, the knowledge about the potential changes of these parameters in the wound bed could be used potentially to predict, and potentially even to control the drug release from the developed wound dressing. The prepared wound dressing was also proven biocompatible towards human skin cells, making it interesting for potential future use in the clinics.

Doxorubicin loaded carboxymethyl cellulose/graphene quantum dot nanocomposite hydrogel films as a potential anticancer drug delivery system.

Creating anticancer properties in the hydrogel film could make it as a candidate for treating cancer tissues. In this work, a novel hydrogel nanocomposite films with anticancer properties were designed via incorporation of graphene quantum dot (GQD) as a nanoparticle into carboxymethyl cellulose (CMC) hydrogel and using doxorubicin (DOX) as drug model with broad-spectrum anticancer properties. Drug release studies carried out at two different pHs and the MTT assay was evaluated for DOX-loaded CMC/GQD nanocomposite hydrogel films against blood cancer cells (K562). The prepared nanocomposite hydrogel films were characterized using Fourier transform infrared (FT-IR), UV-Vis spectroscopy, scanning electron microscopy (SEM), permeability and mechanical properties. The prepared CMC/GQD nanocomposite hydrogel films showed an improvement in vitro swelling, degradation, water vapor permeability and pH-sensitive drug delivery properties along with not significant toxicity against blood cancer cells (K562). According to the obtained results, this nanocomposite hydrogel films can be proposed to use as an anticancer film and drug delivery system.

Osmoprotectants, carboxymethylcellulose and hyaluronic acid multi-ingredient eye drop: a randomised controlled trial in moderate to severe dry eye.

PurposeTo assess the safety and efficacy of an eye drop combining osmoprotectants, carboxymethylcellulose and hyaluronic acid (O/CMC/HA) in reducing symptomatic, moderate to severe dry eye, compared with HA.MethodsIn this investigator-masked, randomised study, patients instilled 1-2 drops/eye of O/CMC/HA or HA (2-6 times/day) for 3 months. Primary endpoint: mean change in Global Ocular Staining Score (GOSS) from baseline at day 35. Noninferiority of O/CMC/HA was tested in the per-protocol population; if achieved, superiority was tested in the intent-to-treat population. Secondary efficacy endpoints: mean change from baseline in GOSS, Ocular Surface Disease Index (OSDI), Schirmer score, tear break-up time (TBUT), corneal/conjunctival staining, conjunctival hyperaemia, symptoms, and patient/investigator assessments.ResultsBaseline characteristics were comparable between groups (n=40 each). O/CMC/HA was noninferior (and not superior) to HA based on similar GOSS reductions from baseline at day 35 and month 3 in both groups (P=0.778, day 35, per-protocol population). Overall, O/CMC/HA and HA provided similar reductions in OSDI, Schirmer score, TBUT, corneal staining and hyperaemia from baseline at 35 days (P≥0.155). More patients reported less severe stinging/burning, sandiness/grittiness, and painful/sore eyes at month 3 with O/CMC/HA (P≤0.039), and more rated the dropper bottle easy to use (87.5%), compared with HA (46.2%; P=0.002). Other patient and investigator assessments were similar between groups. O/CMC/HA and HA were well tolerated.ConclusionsO/CMC/HA is noninferior to HA in improving objective signs of dry eye, with potential advantages for subjective symptoms and patient acceptance.

Torsemide Fast Dissolving Tablets: Development, Optimization Using Box-Bhenken Design and Response Surface Methodology, In Vitro Characterization, and Pharmacokinetic Assessment.

The present study planed to develop new fast dissolving tablets (FDTs) of torsemide. Solid dispersions (SDs) of torsemide and sorbitol (3:1) or polyvinylpyrrolidone (PVP) k25 were prepared. The prepared SDs were evaluated for in-vitro dissolution. Fourier transform infrared spectroscopy and differential scanning calorimetry for SDs revealed no drug/excipient interactions and transformation of torsemide to the amorphous form. Torsemide/sorbitol SD was selected for formulation of torsemide FDTs by direct compression method. Box-Bhenken factorial design was employed to design 15 formulations using croscarmellose sodium and crospovidone at different concentrations. The response surface methodology was used to analyze the effect of changing these concentrations (independent variables) on disintegration time (Y1), percentage friability (Y2), and amount torsemide released at 10 min. The physical mixtures of torsemide and the used excipients were evaluated for angle of repose, Hausner's ratio, and Carr's index. The prepared FDTs tablets were evaluated for wetting and disintegration time, weight variation, drug content, percentage friability, thickness, hardness, and in vitro release. Based on the in-vitro results and factorial design characterization, F10 and F7 were selected for bioavailability studies following administration to Albino New Zealand rabbits. They showed significantly higher C max and (AUC0-12) and shorter T max than those obtained after administration of the corresponding ordinary commercial Torseretic ® tablets. Stability study was conducted for F10 that showed good stability upon storage at 30°C/75% RH and 40°C/75% RH for 3 months.

Experimental Design for Determination of Effects of Superdisintegrant Combinations on Liquisolid System Properties.

The preparation of liquisolid systems presents a promising and innovative possibility for enhancing dissolution profiles and improving the bioavailability of poorly soluble drugs. This study aims to evaluate the differences in the properties of liquisolid systems containing combinations of 3 commercially used superdisintegrants (sodium starch glycolate, crospovidone, and croscarmellose sodium). Multiple regression models and contour plots were used to study how the amount and the type of superdisintegrant used affected the quality parameters of liquisolid tablets. The results revealed that an increased amount of crospovidone in the mixture improves disintegration and wetting time and enhances drug release from the prepared liquisolid tablets. Moreover, it was observed that a binary blend of crospovidone and sodium starch glycolate improved tablet disintegration. Considering the obtained results, it could be stated that crospovidone showed the best properties to be used as superdisintegrant for the preparation of liquisolid systems containing rosuvastatin.

Enhancing Tumor Cell Response to Chemotherapy through the Targeted Delivery of Platinum Drugs Mediated by Highly Stable, Multifunctional Carboxymethylcellulose-Coated Magnetic Nanoparticles.

The fabrication of nanoparticles using different formulations, and which can be used for the delivery of chemotherapeutics, has recently attracted considerable attention. We describe herein an innovative approach that may ultimately allow for the selective delivery of anticancer drugs to tumor cells by using an external magnet. A conventional antitumor drug, cisplatin, has been incorporated into new carboxymethylcellulose-stabilized magnetite nanoparticles conjugated with the fluorescent marker Alexa Fluor 488 or folic acid as targeting agent. The magnetic nanocarriers possess exceptionally high biocompatibility and colloidal stability. These cisplatin-loaded nanoparticles overcome the resistance mechanisms typical of free cisplatin. Moreover, experiments aimed at the localization of the nanoparticles driven by an external magnet in a medium that mimics physiological conditions confirmed that this localization can inhibit tumor cell growth site-specifically.

Novel in situ gelling ocular inserts for voriconazole-loaded niosomes: design, in vitro characterisation and in vivo evaluation of the ocular irritation and drug pharmacokinetics.

This work aimed to develop voriconazole in situ gelling ocular inserts loaded with niosomal suspension. Niosomes and mixed niosomes were prepared using span 40 and span 60 with pluronic L64 and pluronic F127. The entrapment efficiency percentages (EE%), mean vesicle size, polydispersity index (PI), zeta potential and in vitro drug release of these niosomes were evaluated. F3-mixed niosomes prepared with span 60 and pluronic L64 was selected, due to its highest EE; optimum vesicle size with smallest PdI and suitable release pattern of the drug (63% after 8 h). In situ ocular inserts were prepared using sodium carboxymethylcellulose (CMC Na) and sodium alginate (ALG) and characterised for surface morphology, surface pH, water uptake, mucoadhesion and in vitro release. ALG in situ ocular insert (S2) was selected for further in vivo evaluation of the ocular irritation and drug pharmacokinetics in the aqueous humour of rabbit's eyes. S2 in situ gelling ocular insert was non-irritant and showed significantly (p < 0.01) higher Cmax, delayed Tmax and increased bioavailability.

The Enhancement of Nasal Drug Absorption From Powder Formulations by the Addition of Sodium Carboxymethyl Cellulose.

For nasal drug absorption, powder formulations can be expected to provide many advantages. The first aim of this study was to examine drug absorption following nasal administration of powder formulations in rats. Pharmaceutical excipients are typically added to most powder formulations. The second aim was to investigate the change in nasal drug absorption of powder formulations in the presence of sodium carboxymethyl cellulose (CMC-Na). Model drugs used were norfloxacin (NFX), warfarin (WF), and piroxicam (PXC). The absorption from bulk powders is different from that of solutions. The absorption of PXC and WF from powder formulations was enhanced compared to those of the other solutions, while that of NFX, which has a low solubility, was decreased, suggesting that the nasal absorption of many drugs, except poorly soluble drugs, is enhanced when they are administered as powder formulations. CMC-Na enhanced the absorption of NFX and PXC. The presence of CMC-Na slightly decreased the absorption of WF. In vitro transepithelial transport from the powder formulation was not affected by the presence of CMC-Na. Furthermore, the nasal retention of the powder formulation was significantly increased in the presence of CMC-Na. In conclusion, the nasal absorption of many drugs, except those that are poorly soluble, can be increased by administering them as a powder formulation and the nasal absorption of the formulation is enhanced further in the presence of CMC-Na.

Lidocaine permeation from a lidocaine NaCMC/gel microgel formulation in microneedle-pierced skin: vertical (depth averaged) and horizontal permeation profiles.

Common local anaesthetics such as lidocaine are administered by the hypodermic parenteral route but it causes pain or anxiety to patients. Alternatively, an ointment formulation may be applied which involves a slow drug diffusion process. In addressing these two issues, this paper aims to understand the significance of the 'poke and patch' microneedle (MN) treatment on skin in conjunction to the lidocaine permeation, and in particular, the vertical (depth averaged) and horizontal (e.g. lateral) permeation profiles of the drug in the skin. The instantaneous pharmacokinetics of lidocaine in skin was determined by a skin denaturation technique coupled with Franz diffusion cell measurements of the drug pharmacokinetics. All pharmacokinetic profiles were performed periodically on porcine skin. Three MN insertion forces of 3.9, 7.9 and 15.7 N were applied on the MN to pierce the skin. For the smaller force (3.9 N), post MN-treated skin seems to provide an 'optimum' percutaneous delivery rate. A 10.2-fold increase in lidocaine permeation was observed for a MN insertion force of 3.9 N at 0.25 h and similarly, a 5.4-fold increase in permeation occurred at 0.5 h compared to passive diffusional delivery. It is shown that lidocaine permeates horizontally beyond the area of the MN-treated skin for the smaller MN insertion forces, namely, 3.9 and 7.9 N from 0.25 to 0.75 h, respectively. The lateral diffusion/permeation of lidocaine for larger MN-treated force (namely, 15.7 N in this work) seems to be insignificant at all recorded timings. The MN insertion force of 15.7 N resulted in lidocaine concentrations slightly greater than control (passive diffusion) but significantly less than 3.9 and 7.9 N impact force treatments on skin. We believe this likelihood is due to the skin compression effect that inhibits diffusion until the skin had time to relax at which point lidocaine levels increase.

Microneedle-assisted permeation of lidocaine carboxymethylcellulose with gelatine co-polymer hydrogel.

PURPOSE: Lidocaine hydrochloride (LidH) was formulated in sodium carboxymethyl cellulose/ gelatine (NaCMC/GEL) hydrogel and a 'poke and patch' microneedle delivery method was used to enhance permeation flux of LidH. METHODS: The microparticles were formed by electrostatic interactions between NaCMC and GEL macromolecules within a water/oil emulsion in paraffin oil and the covalent crosslinking was by glutaraldehyde. The GEL to NaCMC mass ratio was varied between 1.6 and 2.7. The LidH encapsulation yield was 1.2 to 7% w/w. LidH NaCMC/GEL was assessed for encapsulation efficiency, zeta potential, mean particle size and morphology. Subsequent in vitro skin permeation studies were performed via passive diffusion and microneedle assisted permeation of LidH NaCMC/GEL to determine the maximum permeation rate through full thickness skin. RESULTS: LidH 2.4% w/w NaCMC/GEL 1:1.6 and 1:2.3 respectively, possessed optimum zeta potential. LidH 2.4% w/w NaCMC/GEL 1:2.3 and 1:2.7 demonstrate higher pseudoplastic behaviour. Encapsulation efficiency (14.9-17.2%) was similar for LidH 2.4% w/w NaCMC/GEL 1:1.6-1:2.3. Microneedle assisted permeation flux was optimum for LidH 2.4% w/w NaCMC/GEL 1:2.3 at 6.1 µg/ml/h. CONCLUSION: LidH 2.4% w/w LidH NaCMC/GEL 1:2.3 crossed the minimum therapeutic drug threshold with microneedle skin permeation in less than 70 min.

A docetaxel-carboxymethylcellulose nanoparticle outperforms the approved taxane nanoformulation, Abraxane, in mouse tumor models with significant control of metastases.

Cellax is a PEGylated carboxymethylcellulose conjugate of docetaxel (DTX) which condenses into a 120-nm nanoparticle, and was compared against the approved clinical taxane nanoformulation (Abraxane®) in mouse models. Cellax increased the systemic exposure of taxanes by 37× compared to Abraxane, and improved the delivery specificity: Cellax uptake was selective to the tumor, liver and spleen, with a 203× increase in tumor accumulation compared to Abraxane. The concentration of released DTX in Cellax treated tumors was well above the IC50 for at least 10 d, while paclitaxel released from Abraxane was undetectable after 24h. In s.c. PC3 (prostate) and B16F10 (melanoma) models, Cellax exhibited enhanced efficacy and was better tolerated compared to Abraxane. In an orthotopic 4T1 breast tumor model, Cellax reduced the incidence of lung metastasis to 40% with no metastasic incidence in other tissues. Mice treated with Abraxane displayed increased lung metastasic incidence (>85%) with metastases detected in the bone, liver, spleen and kidney. These results confirm that Cellax is a more effective drug delivery strategy compared to the approved taxane nanomedicine.

Mechanochemically induced disordered structures of vincamine: the different mediation of two cross-linked polymers.

The aims of this research were to prepare highly bioavailable binary cogrounds (vincamine-AcDiSol(®) or PVP-Cl) by means of a mechanochemical process and to study the mediation of each polymer in the induction of physical transformations of the drug. From a set of fifteen cogrounds for each crosslinked polymer, two samples were selected in each group on the basis of the AUC of in vitro dissolution profiles with the help of a statistical comparison. The chosen samples were analysed by means of TEM, XRPD, Raman-spectroscopy/imaging, SSNMR, also including the study of (1)H spin-lattice relaxation times. The research encompassed in vivo oral absorption studies in rats, pharmacokinetic analysis and physical stability studies during 1 year. An intimate drug-polymer mixing was found in the coground samples with domain average dimensions smaller than 100 Å; this reflected in a remarkable enhancement of the in vitro and in vivo bioavailability. Different disordered states were detected in the coground samples as a function of cogrinding time and the type and amount of polymer used. Though both crosslinked polymers produced a remarkable enhancement of the oral bioavailability, coground systems based on AcDiSol(®) are preferable in terms of pharmacokinetic performance and physical stability.

Direct entry of gadolinium into the vestibule following intratympanic applications in Guinea pigs and the influence of cochlear implantation.

Although intratympanic (IT) administration of drugs has gained wide clinical acceptance, the distribution of drugs in the inner ear following IT administration is not well established. Gadolinium (Gd) has been previously used as a marker in conjunction with magnetic resonance imaging (MRI) to visualize distribution in inner ear fluids in a qualitative manner. In the present study, we applied gadolinium chelated with diethylenetriamine penta-acetic acid (Gd-DTPA) to the round window niche of 12 guinea pigs using Seprapack(TM) (carboxlmethylcellulose-hyaluronic acid) pledgets which stabilized the fluid volume in the round window niche. Gd-DTPA distribution was monitored sequentially with time following application. Distribution in normal, unperforated ears was compared with ears that had undergone a cochleostomy in the basal turn of scala tympani and implantation with a silastic electrode. Results were quantified using image analysis software. In all animals, Gd-DTPA was seen in the lower basal scala tympani (ST), scala vestibuli (SV), and throughout the vestibule and semi-circular canals by 1 h after application. Although Gd-DTPA levels in ST were higher than those in the vestibule in a few ears, the majority showed higher Gd-DTPA levels in the vestibule than ST at both early and later time points. Quantitative computer simulations of the experiment, taking into account the larger volume of the vestibule compared to scala tympani, suggest most Gd-DTPA (up to 90%) entered the vestibule directly in the vicinity of the stapes rather than indirectly through the round window membrane and ST. Gd-DTPA levels were minimally affected by the implantation procedure after 1 h. Gd-DTPA levels in the basal turn of scala tympani were lower in implanted animals, but the difference compared to non-implanted ears did not reach statistical significance.

Effect of sodium carboxymethylcellulose and fucidic acid on the gel characterization of polyvinylalcohol-based wound dressing.

The purpose of this study was to investigate the effect of sodium carboxymethylcellulose (Na-CMC) and fucidic acid on the gel characterization for the development of sodium fucidate-loaded wound dressing. The cross-linked hydrogel films were prepared with polyvinyl alcohol (PVA) and sodium carboxymethylcellulose (Na-CMC) using the freeze-thawing method. Their gel properties such as gel fraction, swelling, water vapor transmission test, morphology, tensile strength and thermal property were investigated. In vitro protein adsorption test and release were performed. Na-CMC decreased the gel fraction and tensile strength of the hydrogels, but increased the swelling ability, water vapor transmission rate, elasticity and porosity of hydrogels. Thus, the wound dressing developed with PVA and Na-CMC was more swellable, flexible and elastic than that with only PVA because of its cross-linking interaction with PVA. However, the drug had a negative effect on the gel properties of hydrogels but there were no significant differences. In particular, the hydrogel composed of 2.5% PVA, 1.125% Na-CMC and 0.2% drug might give an adequate level of moisture and build up the exudates on the wound area. Thus, this sodium fucidate-loaded hydrogel could be a potential candidate for wound dressing with excellent forming.

Formulations and delivery vehicles for bone morphogenetic proteins: latest advances and future directions.

Growth factors are essential components of the diamond concept model. The bone morphogenetic proteins (BMPs) are the most potent and promising growth factors and their clinical efficacy is well demonstrated for specific indications. Application of BMPs involves a carrier material to enhance local residual time and pharmacokinetics. On the other hand carrier materials, collagen at this point, also limit the use of BMPs, for example in minimally invasive application methods. In this overview, the pharmacokinetics of BMPs, and various carrier materials (collagen, synthetic polymers, calcium phosphates, hyaluronic acid, CMC, and sodium acetate) are discussed. No other carrier material than collagen has been proven effective in clinical studies. Other formulations are needed to improve the residual time and handling.