Textural Analysis and Flow Rheometry of Novel,Bioadhesive Antimicrobial Oral Gels

Purpose. This study examined the rheological and textural characteristics (hardness, compressibilty, adhesiveness and cohesiveness) of bioadhesive oral gels containing the antimicrobial agent chlorhexidine. Methods. Textural analysis was performed using a Stable Micro Systems texture analyser (model TA-XT 2) in texture profile analysis (TPA) mode. In this, an analytical probe was twice compressed into each formulation to a defined depth (15 mm) and at defined rates (2, 4, 6, 8, 10 mm s^–1), allowing a delay period (15 s) between the end of the first and beginning of the second compressions. Flow rheograms were performed using a Carri-Med CSL²-100 rheometer with parallel plate geometry under controlled shearing stresses at 20.0 ± 0.1°C. Results. All formulations exhibited pseudoplastic flow with thixotropy. Increasing concentrations of each polymer significantly increased formulation hardness, compressibility, adhesiveness and zero-rate viscosity. Increased hardness and compressibility were due to the attendent increased viscosities of these formulations. Increased adhesiveness was related to the concentrations of the (bioadhesive) polymers employed in these formulations and, in addition, was dependent on the physical state of polycarbophil. Formulation viscosity contributed to product adhesiveness, reflecting the importance of product rheology on this parameter. Decreased formulation cohesiveness, observed as the concentrations of the PVP, PC and HEC (3–5%w/w) were increased, was due an increase in semi-solid character. Numerical values of hardness, compressibility and adhesiveness were affected by the choice of probe speed, a parameter related to rate of shear in flow rheometry. Statistical interactions were observed and were assigned to the effects of HEC on the physical state of PVP (dissolved or dispersed) and PC (swollen or unswollen). Conclusions. This study has demonstrated both the applicability of textural analysis for the mechanical characterisation of bioadhesive semi-solid gel systems and, additionally, the direct influence of viscosity on the parameters defined by textural analysis, namely, hardness, compressibility and adhesiveness.     

Physicochemical characterization and preliminary in vivo efficacy of bioadhesive, semisolid formulations containing flurbiprofen for the treatment of gingivitis.

In this study, the physicochemical properties and preliminary in vivo clinical performance of formulations containing hydroxyethylcellulose (HEC; 3, 5, 10% w/w), poly(vinylpyrrolidone) (PVP; 3, 5% w/w), polycarbophil (PC; 1, 3, 5% w/w), and flurbiprofen (5% w/w) were examined. Flurbiprofen release into PBS pH 7.4 was performed at 37 degrees C. The mechanical properties (hardness, compressibility, adhesiveness, initial stress) and syringeability of formulations were determined using a texture analyzer in texture profile analysis (TPA) and compression modes, respectively. In general, the time required for release of 10 and 30% of the original mass of flurbiprofen (t10%, t30%) increased as the concentration of each polymeric component increased. However, in the presence of either 5 or 10% HEC and 5% PC, increased PVP concentration decreased both t10%, t30% due to excessive swelling (and disintegration) of these formulations. Increased concentrations of HEC, PVP, and PC significantly increased formulation hardness, compressibility, work of syringe expression, and initial stress due to the effects of these polymers on formulation viscoelasticity. Similarly, increased concentrations of PC (primarily), HEC, and PVP increased formulation adhesiveness due to the known bioadhesive properties of these polymers. Clinical efficacies of formulations containing 3% HEC, 3% PVP, 3% PC, and either 0% (control) or 5% (test) flurbiprofen, selected to offer optimal drug release and mechanical properties, were evaluated and clinically compared in an experimental gingivitis model. The test (flurbiprofen-containing) formulation significantly reduced gingival inflammation, as evaluated using the gingival index, and the gingival crevicular fluid volume, whereas, these clinical parameters were generally increased in volunteers who had received the control formulation. There were no observed differences in the plaque indices of the two subject groups, confirming that the observed differences in gingival inflammation could not be accredited to differences in plaque accumulation. This study has shown both the applicability of the in vitro methods used, particularly TPA, for the rational selection of formulations for clinical evaluation and, additionally, the clinical benefits of the topical application of a bioadhesive semisolid flurbiprofen-containing formulation for the treatment of experimental gingivitis.     

Rheological characterization of bioadhesive, antimicrobial, semisolids designed for the treatment of periodontal diseases: transient and dynamic viscoelastic and continuous shear analysis.

This study examined the creep behavior and oscillatory and flow properties of tetracycline-containing, bioadhesive semisolid formulations, designed for localized treatment of periodontal disease. Formulations were prepared containing hydroxyethylcellulose (HEC, 1, 3, or 5% w/w), poly(vinylpyrrolidone) (PVP, 2 or 3% w/w), polycarbophil (PC, 1 or 3% w/w), and tetracycline (5% w/w, as the hydrochloride). In creep analysis, each formulation exhibited several distinct regions that were mathematically modelled using a multi-element Voigt model with a residual spring and dashpot. Increasing the concentrations of each polymeric component decreased the elastic compliance (J(0)) yet increased the residual viscosity. In oscillatory analysis, increased polymer concentrations increased the storage modulus (G'), the loss modulus (G") and the dynamic viscosity (eta'), yet decreased the loss tangent (tan delta). The relationships between G' or G" and frequency were observed to plateau at higher frequencies, which is indicative of polymer chain entanglement and network formation. With the exception of formulations containing 1% HEC, the formulations were elastic (tan delta < 1), with large G' and small J(0) values. All formulations exhibited pseudoplastic flow with thixotropy. Increasing concentrations of each polymeric component increased the zero-shear viscosity (determined using the Cross model) and was further evidence of polymer chain entanglement. Formulations containing 1% w/w HEC possessed excellent flow properties, however, their thixotropic behavior and essentially elastoviscous nature (large J(0) and tan delta) would be disadvantageous for use in the treatment of periodontal disease because of rapid removal from the pocket and relatively uncontrolled drug release. Despite their advantageous viscoelastic properties, the flow properties of formulations containing 5% w/w HEC were inappropriate, rendering administration through a periodontal syringe potentially difficult. Based on their rheological behavior, formulations containing HEC (3% w/w), PVP (2 or 3% w/w), and PC (1 or 3% w/w) would be suitable for clinical application. However, consideration of other physicochemical properties (e.g., bioadhesion, drug release kinetics) must be performed prior to selection of the most suitable formulation for clinical examination. This study has highlighted the successful complimentary application of creep analysis and oscillatory and flow rheometry for the characterization and development of bioadhesive semisolid formulations for the treatment of periodontal disease.     

In Vitro-In Vivo Evaluation of a Controlled Release Buccal Bioadhesive Device for Oral Drug Delivery

Purpose. To investigate the use of buccal bioadhesive device in targeting controlled drug delivery to the gastrointestinal tract. Methods. A three-leg crossover study was designed to evaluate the application of buccal bioadhesive device for providing controlled drug delivery to the gastrointestinal tract of a model drug cyanocobalamin in four healthy adult male beagle dogs. Results. In vitro dissolution studies using deionized water as the medium indicated that 100% of the drug was released within 15 min from a immediate release oral capsule formulation, whereas 90% of the drug was released within a period of 18 hrs from a buccal bioadhesive device formulation. Drug release from the buccal bioadhesive devices appeared to follow Higuchi's square root of time dependent model. The terminal half-life of the drug following I.V. administration in four dogs was found to be 16.4 ± 2.4 hrs. Following immediate release oral capsule administration of the drug C_max, t_max and bioavailability were 2333 ± 1469 ng/L, 2.5± 1.0 hrs and 14.1 ± 7.9%, respectively. Following buccal bioadhesive device administration of the drug C_max, t_max and bioavailability were 4154 ± 1096 ng/L, 11 ± 1.2 hrs and 35.8 ± 4.1%, respectively. Significantly higher bioavailability of the drug was observed with the buccal bioadhesive device administration when compared to the immediate release oral capsule. Conclusions. The buccal bioadhesive device appears to improve the oral bioavailability of cyanocobalamin by providing controlled delivery of the drug to the gastrointestinal tract.     

Formulation and characterisation of tetracycline-containing bioadhesive polymer networks designed for the treatment of periodontal disease

This study described the drug release, rheological (dynamic and flow) and textural/mechanical properties of a series of formulations composed of 15% w/w polymethylvinylether-co-maleic anhydride (PMVE-MA), 0-9% w/w polyvinylpyrrolidone (PVP) and containing 1-5% w/w tetracycline hydrochloride, designed for the treatment of periodontal disease. All formulations exhibited pseudoplastic flow with minimal thixotropy. Increasing the concentration of PVP sequentially increased the zero-rate viscosity (derived from the Cross model) and the hardness and compressibility of the formulations (derived from texture profile analysis). These affects may be accredited to increased polymer entanglement and, in light of the observed synergy between the two polymers with respect to their textural and rheological properties, interaction between PVP and PMVE-MA. Increasing the concentration of PVP increased the storage and loss moduli yet decreased the loss tangent of all formulations, indicative of increased elastic behaviour. Synergy between the two polymers with respect to their viscoelastic properties was observed. Increased adhesiveness, associated with increased concentrations of PVP was ascribed to the increasing bioadhesion and tack of the formulations. The effect of increasing drug concentration on the rheological and textural properties was dependent on PVP concentration. At lower concentrations (0, 3% w/w) no effect was observed whereas, in the presence of 9% w/w PVP, increasing drug concentration increased formulation elasticity, zero rate viscosity, hardness and compressibility. These observations were ascribed to the greater mass of suspended drug in formulations containing the highest concentration of PVP. Drug release from formulations containing 6 and 9% PVP (and 5% w/w drug) was prolonged and swelling/diffusion controlled. Based on the drug release, rheological and textural properties, it is suggested that the formulation containing 15% w/w PMVE-MA, 6% w/w PVP and tetracycline hydrochloride (5% w/w) may be useful for the treatment of periodontal disease.     

Development and Physical Characterization of a Periodontal Bioadhesive Gel of Metronidazole

To develop a localized drug delivery system that offers prolonged administration of metronidazole into the periodontal pocket, muccoadhesive gel formulations containing 5% w/w metronidazole were prepared using the bioadhesive polymers: carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, polyvinylpirrolidone, and carbopol. Increased concentrations of the polymers decreased the drug release rate and enhanced syringeability, yield value, and adhesiveness but decreased the spreadability. The bioadhesive properties of the gels were affected by pH and Ca 2+ concentration. The gel containing 20% hydroxyethylcellulose, 20% polyvinylpirrolidone, and 1% carbopol exhibited zero-order drug release kinetics and suitable physical properties for drug delivery to the periodontal pocket.     

Development and physical characterization of a periodontal bioadhesive gel of metronidazole

To develop a localized drug delivery system that offers prolonged administration of metronidazole into the periodontal pocket, muccoadhesive gel formulations containing 5% w/w metronidazole were prepared using the bioadhesive polymers: carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, polyvinylpirrolidone, and carbopol. Increased concentrations of the polymers decreased the drug release rate and enhanced syringeability, yield value, and adhesiveness but decreased the spreadability. The bioadhesive properties of the gels were affected by pH and Ca 2+ concentration. The gel containing 20% hydroxyethylcellulose, 20% polyvinylpirrolidone, and 1% carbopol exhibited zero-order drug release kinetics and suitable physical properties for drug delivery to the periodontal pocket.     

Formulation development of novel in situ nanoemulgel (NEG) of ketoprofen for the treatment of periodontitis

The aim of the present study was to formulate and evaluate in situ gelling syringeable nanoemulgels (NEGs) of ketoprofen for periodontal delivery. Application of 3-factor 3-level design was employed using the Box–Behnken experimental design for the optimization of nanoemulsion using three independent variables such as percent concentration (v/v) of oil (X₁), S_mix (mixture of surfactant and cosurfactant) (X₂) and water (X₃); while the particle size (nm) (Y₁), polydispersity index (Y₂) and zeta potential (mV) (Y₃) were used as dependent variables. The NEG was evaluated based on their drug content, pH measurement, mucoadhesion on the goat buccal mucosa, syringeability and inverted sol-gel transition temperature. The drug release data were analyzed for curve fitting based on the Korsmeyer–Peppas law, and the n-values of optimized A5 and A8 formulations were found 0.3721 and 0.3932, respectively, confirmed that both the formulations followed pseudo Fickian diffusion (n?<?0.43). The formulation A8 with the optimal drug release was identified as the best NEG formulation. Results of rheological, mucoadhesion and syringeability studies showed the suitability of desired sol-gel property for periodontal drug delivery. The Herschel–Bulkley model was the best fit model to explain the flow behavior of optimized formulation. Using the HET-CAM method, significantly lower in vitro toxicity was indicated the suitability of developed NEG for intra-pocket delivery.     

Formulation,in-vitro characterization and clinical evaluation of curcumin in-situ gel for treatment of periodontitis

This study aimed to develop syringeable in-situ curcumin (cur) gel for the treatment of periodontal pockets as well as to evaluate the clinical efficacy of Cur in-situ gel formulation. Different in-situ gel formulations of Cur were prepared using 30% of pluronic F127, and 1% of carbopol P934. The formulations were evaluated regarding gelation temperature, pH, viscosity, syringeability study, in-vitro release and chemical stability of cur. The effect of aging of gel formulations for 3months in refrigerator was investigated. The selected formulation was clinically evaluated through the determination of probing depth, plaque index, and bleeding index at baseline and 1 month after application. The formulations showed accepted gelation temperature ranging from 28 to 34?°C and all had pH value of 4. The viscosity of the formulations at 4?°C ranged from 19 000 to 37 000 cP. All formulations were easily syringeable through 21 gauge needle at cold temperature. Curcumin stability during the release study was maintained. Aging showed no significant effect on release profile, drug content, or the pH after 3 months, while it showed a slight increase in viscosity with concomitant decrease in gelation temperature. Selected formulations delivered into periodontal pocket evaluated clinically showed to be effective. The treated group revealed that the adjunctive use of intracrevicular 2% curcumin in-situ gel adjunct to mechanical treatment in patients with adult periodontitis could aid in significant clinical reduction of probing depth, bleeding index, and to less extent of plaque. This indicates that curcumin in this novel drug delivery system is an excellent candidate for periodontal disease treatment.     

Formulation and preliminary in vivo dog studies of a novel drug delivery system for the treatment of periodontitis

A novel drug delivery system for the treatment of periodontitis was developed using two components. The first was tetracycline base loaded into the microtubular excipient halloysite, which was coated with chitosan to further retard drug release. Encapsulation efficiencies of 32.5% were achieved with the loading procedure, with tetracycline base showing in vitro release for up to 50 days in simulated gingival crevicular fluid. The second component developed was a vehicle for the drug loaded coated halloysite, which was primarily based on the thermoresponsive polymer, poloxamer 407. A concentration of 20% was chosen with the thermoresponsivity of the system modified using PEG 20,000 so that the mobile product at room temperature would gel by temperature rise following syringing into a periodontal pocket. Retention of the overall system in the pocket was further improved by the addition of octyl cyanoacrylate (OCA). The thermoresponsivity of the poloxamer 407 system proved to be sensitive to the presence of added excipients with the levels of PEG 20,000 and OCA requiring modification in the presence of the halloysite component. A final formulation was developed which consisted of 200 mg of halloysite double loaded with tetracycline base and coated with chitosan, suspended in 1 ml of poloxamer 407 20% (w/w), PEG 20,000 0.5% (w/w), OCA 1.0% (w/w), water to 100%, adjusted to pH 4. The syringeability of this formulation at various temperatures was evaluated to ensure ease of delivery to the periodontal pocket. A stability study was performed to examine the change in thermoresponsivity over time, with the final formulation found to be stable for at least 9 months when stored at room temperature (approximately 20 degrees C). This formulation offered ease of delivery to the periodontal pocket and sustained release of the antibiotic for up to 6 weeks. The formulation had preliminary in vivo testing performed in dogs to determine levels of drug release, antimicrobial activity and retentive ability of the product. A wound pocket creation model was developed for the purposes of the trial. The product was easy to deliver to the pockets with application times of less than 1 min. Results showed the product was retained in the pocket for up to 6 weeks with effective tetracycline levels released locally over this time period, which achieved good antibacterial activity.     

Properties of bioadhesive ketoprofen liquid suppositories: preparation,determination of gelation temperature,viscosity studies and evaluation of mechanical properties using texture analyzer by 4 × 4 factorial design

Abstract

Context: Development and evaluation of thermosensitive and bioadhesive liquid suppositories containing ketoprofen (KP).

Objective: This study was conducted to develope thermosensitive and bioadhesive liquid suppositories containing KP using poloxamer and different bioadhesive polymers and to investigate their gelation temperature, viscosity and mechanical properties.

Materials and methods: Bioadhesive liquid suppositories were prepared by the cold method using poloxamer 407 (P 407), Poloxamer 188 (P 188) and various amounts of different bioadhesive polymers. Their gelation temperatures, viscosity values and mechanical properties were determined using texture analyzer by 4?×?4 factorial design.

Results: It was seen that in presence of KP, gelation temperature of formulation P 407/P 188 (4/20%) significantly decreased from 64 to 37.1?°C. It is to be noted that addition of increasing concentrations of bioadhesive polymers lowered gelation temperature and its decrease was highest with addition of Carbopol 934 P (C). Results of texture profile analysis (TPA) showed that formulations containing C have significantly higher hardness and adhesiveness values than other bioadhesive formulations. According to TPA, gel structure of liquid suppository formulation F5, containing P 407/P 188/KP/C (4/20/2.5/0.8%), exhibited the greatest hardness, compressibilty, adhesiveness and besides greatest viscosity.

Discussion and conclusion: According to mechanical properties and viscosity values, it was concluded that F5 could be a promising formulation.     

Viscoelastic Properties of Bioadhesive,Chlorhexidine-Containing Semi-Solids for Topical Application to the Oropharynx

Purpose. This study examined the viscoelastic properties of bioadhesive, chlorhexidine-containing semi-solid formulations, designed for topical application to the oropharynx. Methods. Oscillatory rheometry was performed using a Carri-Med CSL²-100 rheometer at 20.0 ± 0.1° C in conjunction with parallel plate geometry (2 cm diameter, 0.5 mm sample thickness). Samples were subjected to a constant strain (6.5 × 10^–3 rad) and defined viscoelastic parameters, namely storage modulus (G), loss modulus (G), loss tangent (tan ) and dynamic viscosity (), measured over a defined frequency range (0.01-1.0 Hz). Results. As the oscillatory frequency was increased, G G of all formulations increased, whereas both and tan significantly decreased. The magnitude of increase of G and G as a function of frequency was relatively small, indicating that, in general, the formulations were non-cross-linked elastic systems. Increasing concentrations of HEC, PVP and PC significantly increased G, G, yet decreased tan observations that may be attributed to the physical state of each polymer in the formulations. Formulation elasticity increased (i.e. tan decreased) as a result of increased entanglement of polymeric chains of dissolved components (i.e. HEC and PVP) and the restrained extension of swollen, cross-linked chains of PC. Additionally, in formulations where the saturation solubility of PVP was exceeded and/or insufficient 'free-water' was available for maximal swelling of PC, formulation elasticity increased as a result of the increasing mass of dispersed solid particles of PVP and/or PC. Formulation increased due to the attendent effects of polymer chain entanglement and polymer state on overall formulation viscosity. Conclusions. Following application to the oropharynx, the formulations will behave as elastic systems. Thus, these formulations would be expected to offer advantageous clinical properties, e.g., prolonged drug release, increased bioadhesion. However, it is noteworthy that the final choice of formulation for clinical evaluation will involve a compromise between viscoelastic characteristics and acceptable textural properties, e.g. ease of product application. This study has shown the applicability of oscillatory rheometry for both the characterisation and selection of candidate, topical bioadhesive formulations for clinical evaluation.     

Improving Relative Bioavailability of Dicumarol by Reducing Particle Size and Adding the Adhesive Poly(Fumaric-Co-Sebacic) Anhydride

Purpose. This study was carried out to show the effect of particle size reduction and bioadhesion on the dissolution and relative bioavailability of dicumarol. Methods. Formulations were produced by a variety of methods including a novel technique to reduce particle size as well as phase inversion with poly(fumaric-co-sebacic)anhydride p(FA:SA) to create nanospheres. Drug was administered to groups of pigs and rats via oral gavage of a suspension, and dicumarol concentration in the blood was measured using a double extraction technique.Results. In vitro results showed improved dissolution in both the micronized formulation and the encapsulated p(FA:SA) nanospheres. In vivo, relative bioavailability of a spray-dried formulation was increased by 17% in the rat and 72% in the pig by further reduction in particle size. The bioadhesive p(FA:SA) formulation also improved relative bioavailability over the spray-dried drug, increasing it by 55% in the rat and 96% in the pig. Additionally, the p(FA:SA) formulation prolonged T_max and decreased C_max in both species. Conclusion. This work demonstrates the importance of particle size and bioadhesion to improve oral bioavailability of ducumarol.     

Pressure-sensitive mucoadhesive polymer-based dental patches to treat periodontal diseases: an in vitro study

Abstract

Local drug delivery for periodontal diseases is still a challenge due to very short residence time, involuntary swallowing and salivary wash-out. Present study is, therefore, an attempt to develop pressure-sensitive adhesive polymers-based mucoadhesive dental patches to ensure satisfactory prolonged release of drugs, to treat periodontal diseases locally. Polymers such as duro-tak® 387-2516 and duro-tak® 387, ethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol along with drugs amoxicillin trihydrate and diclofenac sodium were used to develop the experimental patches. The patches were characterized for mass variation, thickness, area, moisture-content and moisture-uptake, folding endurance, structural integrity in simulated saliva, bioadhesive strength, surface pH, scanning electron microscopy, cellular morphology, in vitro drug release and temperature-dependant stability study as per ICH guideline. Incorporation of release enhancers in the patches improved drug release. Drugs released in a sustained manner due to the formation of physical bonds between the polymers (as assessed by FTIR study) which might alter the length of drug diffusion pathways. The formulation F3 with tween 80 as release enhancer provided best drug release profile over the period of 8?h, thus it could be a successful attempt for the management of oral pathogens and dental pain.     

Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design

Smart gel periodontal drug delivery systems (SGPDDS) containing gellan gum (0.1–0.8% w/v), lutrol F127 (14, 16, and 18% w/v), and ornidazole (1% w/v) were designed for the treatment of periodontal diseases. Each formulation was characterized in terms of in vitro gelling capacity, viscosity, rheology, content uniformity, in vitro drug release, and syringeability. In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.8% w/v of gellan gum and 16% w/v of lutrol F127 exhibited superior physical characteristics.     

尼莫地平微粉化物双层渗透泵控释片的制备

目的 制备尼莫地平微粉化物双层渗透泵控释片。方法 以尼莫地平为模型药物,将微粉化增溶技术应用于控释双层渗透泵剂型中,设计并制备体外控释12 h的尼莫地平双层渗透泵片,采用相似因子法（f₂）对不同处方释药行为的相似性进行评价,并对处方进行优化。结果 成功制备了尼莫地平微粉化物双层渗透泵控释片,零级释放特征明显,符合渗透泵的释药机制。结论 将微粉化增溶技术与控释双层渗透泵技术相结合,显著提高了难溶性药物尼莫地平的体外释放,成功制备了控释制剂。     

Novel neomycin sulfate-loaded hydrogel dressing with enhanced physical dressing properties and wound-curing effect

To develop a novel neomycin sulfate-loaded hydrogel dressing (HD), numerous neomycin sulfate-loaded HDs were prepared with various amounts of polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP) and sodium alginate (SA) using freeze-thawing technique, and their physical dressing properties, drug release, in vivo wound curing and histopathology in diabetic-induced rats were assessed. SA had a positive effect on a swelling capacity, but a negative effect on the physical dressing properties and drug release of HD. However, PVP did the opposite. In particular, the neomycin sulfate-loaded HD composed of drug, PVA, PVP and SA at the weight ratio of 1/10/0.8/0.8 had excellent swelling and bioadhesive capacity, good elasticity and fast drug release. Moreover, this HD gave more improved wound curing effect compared to the commercial product, ensured the disappearance of granulation tissue and recovered the wound tissue to normal. Therefore, this novel neomycin sulfate-loaded HD could be an effective pharmaceutical product for the treatment of wounds.     

不同载体对缬沙坦纳米骨架载药系统溶出行为和生物利用度影响的研究

目的 通过调节纳米骨架载药系统（NDDS）中载体类型和比例实现对缬沙坦体外溶出和体内生物利用度的调控。方法 以缬沙坦作为模型药物,分别选取酸性敏感材料Eudragit E100（E100）、碱性敏感材料Eudragit L100-55（L100-55）作为载体材料,介孔二氧化硅Sylysia 350（S350）、Aerosil 200（A200）作为纳米骨架,通过调节载体和骨架材料的类型和比例筛选出具有pH 1.2、6.8敏感释放行为的纳米骨架载体处方,考察缬沙坦在pH 1.2、6.8环境中释放和在大鼠体内的药动学行为特征。结果 筛选的pH 1.2敏感释放缬沙坦NDDS处方缬沙坦、S350、E100比例为1∶3∶1,pH 6.8敏感释放缬沙坦NDDS处方为缬沙坦、A200、L100-55比例为1∶1∶3。pH 6.8敏感释放处方可调控缬沙坦在肠道pH 6.8条件下特异性溶出;pH 1.2敏感释放处方在保持缬沙坦在pH 6.8高溶出特性的同时可特异性地提高胃部酸性条件下的药物释放。pH 1.2、6.8敏感释放缬沙坦NDDS均一定程度上改善了缬沙坦的生物利用度,其中pH 6.8敏感释放缬沙坦NDDS提高生物利用度的幅度更高,血药浓度变化比较平缓。结论 NDDS可以调控缬沙坦的体外溶出和生物利用度,有望应用于pH值敏感性难溶药物的递送。     

Aminoalcohol esters of hydroxyboranes. 10. Tetracycline boron Mannich bases as potential antineoplastic agents

Aminoalcohol Esters of Hydroxyboranes, X: Boron Mannich Bases of Tetracycline: Potential Antitumor Agents The synthesis of the boron-containing N-Mannich bases 1 of tetracycline, paraformaldehyde and boron-heterocycles is reported. The condensation product 2 of phenylboronic acid with tetracycline is described. Compound 1b may show some activity against Leukemia P388.     

In situ gelling, bioadhesive nasal inserts for extended drug delivery: in vitro characterization of a new nasal dosage form.

The purpose of this study was the preparation and characterization of sponge-like, in situ gelling inserts based on bioadhesive polymers. Hydrophilic polymers (carrageenan, Carbopol, chitosan, hydroxypropyl methylcellulose (HPMC) K15M and E5, sodium alginate, sodium carboxy methylcellulose (NaCMC), polyvinyl pyrrolidone (PVP) 90, xanthan gum) were dissolved with/without the model drug oxymetazoline HCl in demineralized water and lyophilized into small inserts. The drug release, water uptake, mechanical properties, X-ray diffraction and bioadhesion potential of the nasal inserts were investigated. A sponge-like structure of nasal inserts was formed with amorphous, but not with crystalline polymers during the freeze-drying process. The insert hardness increased with the glass transition temperature of the polymer (PVP25相似文献