Application of hot-melt coating for controlled release of propranolol hydrochloride pellets

Waxes are available in various lyophilicity, and they can be used to regulate the release from multiunit-controlled release pellets. In this study, the application of saturated polyglycolysed glyceride (Gelucire® 50/02) and glycerol palmitostearate (Precirol® ATO5) as drug release regulators for propranolol pellets and the kinetics of release were investigated. Propranolol pellets containing 60% microcrystalline cellulose (Avicel® PH101) were prepared by using direct pelletization technique in a fluidized-bed rotary granulator (Glatt GPCG1). The pellets of 16:18 mesh size were collected and coated with the molten wax(es) at various ratios and thicknesses in a fluidized-bed top spray coater (Glatt GPCG1). The dissolution was determined using test method for Propranolol Extended Release Capsules USP 24 and was found to be very rapid with the uncoated pellets. The dissolution of coated pellet was decreased with the increases in Precirol ATO5 proportion and coating thickness. Plot of log % drug release vs. reciprocal of time showed a good linear relationship. The k value derived from the slope of the plot and designated as a “diffusive resistance constant” linearly increased with the coating level. The findings indicated that drug release could be adjusted by varying the ratio of Precirol® ATO5 to Gelucire® 50/02 as well as the thickness of the coat.     

Effect of microorganisms during the initial coagulum maturation of Hevea natural rubber

The involvement of microorganisms in the initial stage of maturation of natural rubber coagula was assessed with five latex treatments that varied in the initial quantity of microorganisms; the treatments ranged from latex added with an antimicrobial agent (3.4 × 10⁴ CFU/mL) to strongly inoculated latex (2.4 × 10⁷ CFU/mL). After 0–6 days of maturation, the obtained rubber was characterized with respect to its physical and structural properties. The Wallace plasticity (P₀) and plasticity retention index (PRI) remained constant during maturation with the antibiotic‐added treatment. PRI decreased with the maturation time, and the rate was proportional to the initial microorganism concentration. P₀ of all inoculated rubber increased for the first 2 days of maturation and decreased after 6 days of maturation. With respect to structural parameters, a higher initial microorganism content corresponded to a higher gel content and a lower weight‐average molar mass after maturation, drying, and storage. The inoculated rubber showed a stable value for the number‐average molar mass (M_n), in contrast to the noninoculated samples, for which an increase in M_n during maturation was observed. The quantity of microorganisms significantly affected the physical properties and structure of the processed dry rubber. The mechanisms occurring during the initial stage of maturation are complex, and microorganisms are involved not only in the increase in sensitivity to thermooxidation but also in the crosslinking phenomenon between isoprene chains. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Design of an i.v. formulation of an unstable prodrug candidate for prostate cancer treatment: solution chemistry of N-(glutaryl-hyp-ala-ser-cyclohexylglycyl-gln-ser-leu)-doxorubicin

The chemical degradation of N-(glutaryl-hyp-ala-ser-cyclohexylglycyl-gln-ser-leu)-doxorubicin (henceforth referred to as doxorubicin peptide conjugate 1) was studied in buffered aqueous solution. The pH-rate profile of degradation shows that the doxorubicin conjugate is most stable between pH 5 and 6. The dependence of log k_obsd on pH in acidic medium is characteristic of specific acid-catalysis of the sugar hemiaminal of 1 (as in the case of doxorubicin). Isolation of degradates and structural determination shows that the degradation at lower pH values yields the water-insoluble aglycone doxorubicinone, supporting the mechanism of acid-catalyzed loss of the amino sugar. At pH higher than 5, a more complicated degradation pattern is observed, including the loss of the amino sugar and the aromatization of the saturated ring to give 7,8-dehydro-9,10-desacetyldoxorubicinone as one of the major products. Around the pH of maximum stability in solution, the rate of degradation of 1 is significantly greater than that for doxorubicin, which rules out the formulation of a room temperature solution product with a sufficiently long shelflife for market use. Design of a stable lyophilized formulation for sterile reconstitution based on the physicochemical properties of 1 is described.     

Toughening polycarbonate with core–shell structured latex particles

The toughness as a function of temperature of polycarbonate modified by blending with core-shell structured latex particles was evalated. Comparisons were made among a commercial core-shell latex (MBS), other core-shell (CS) latexes that incorporated a single component rubbery core, and a new class of interpenetrating polymer network (IPN) core-shell latexes with two elastomers in the core. Notched tensile tests differentiated among the blends in terms of their toughness. The most effective modifier at low temperatures was the commercial MBS latex. The CS latexes produced blends that were only slightly less tough than the MBS blends despite better dispersion of MBS and better adhesion to the matrix. The IPN blends were the least tough at low temperatures; however, at 25°C, a blend with IPN had the highest impact strength. Differences between CS and MBS blends were attributed to differences in the percent of butadiene-containing rubber and the chemical nature of the shell. A comparison among the CS latexes showed that increasing the acrylonitrile content of the shell increased the toughness, and increasing the rubber content or the gel fraction of the core increased the toughness. © 1996 Wiley & Sons, Inc.     

Polyurethane foams from oligomers derived from waste tire crumbs and polycaprolactone diols

This work was an initial study on the synthesis of polyurethane foams (PUF) by using diols obtained from the controlled degradation of waste tire crumbs and from polycaprolactone (PCL) followed by examination of their biodegradability. Natural rubber (NR, cis?1,4 polyisoprene) and butadiene rubber (BR) chains contained in waste tire crumbs were chemically modified into carbonyl telechelic (CTWT) and successively into hydroxyl telechelic oligomers (HTWT). Four types of PUF were prepared with different molar ratios between the HTWT and the PCL diols. CTWT and HTWT were analyzed by ¹H‐NMR, SEC, and FT‐IR to confirm their chemical structure. Formation of the urethane bond was demonstrated by FT‐IR spectra. The addition of the PCL diol increased the thermal degradation temperature of the PUF based on thermogravimetric analysis. According to scanning electron microscopy, polyhedral closed cells were obtained. The molar ratio of HTWT/PCL diols strongly affected the kinetic rate of foam formation and foam morphology. A low kinetic rate provided PUF with a high density, small cell size, and a broad cell size distribution. In order to assess biodegradation of PUF, the modified Sturm test was carried out for 60 days at ambient temperature (27–30 °C). The biodegradation of PUF containing only HTWT was 31.2% and 51.3% at 28 days and 60 days of testing, respectively whereas the PUF containing 1/0.5 HTWT/PCL diols (by mole) showed a higher biodegradation: 39.1% and 64.3% at 28 days and 60 days of testing respectively. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44251.     

Enhancement of the Skin Permeation of Clindamycin Phosphate by Aerosol OT/1-Butanol Microemulsions

Microemulsions of water/isopropyl palmitate (IPP)/Aerosol OT (AOT)/1-butanol were developed as alternative formulations for topical delivery of clindamycin phosphate. Effect of AOT:1-butanol ratios on microemulsion region existence in the pseudoternary phase diagrams was investigated. The 2:1 AOT:1-butanol provided the largest microemulsion region. Five microemulsions of 1% w/w clindamycin phosphate were prepared and characterized. The permeation through human epidermis of the microemulsions was evaluated and compared with the 70% isopropanol solution using modified Franz diffusion cells. The drug permeation from all microemulsions was found to be significantly greater than that from the solution, indicating the enhancement of the skin permeation by the microemulsions. Within the same microemulsion type, the drug permeation increased with increasing the amount of AOT:1-butanol. The drug permeation from oil-in-water (o/w) microemulsions was relatively higher than that from water-in-oil (w/o) microemulsions. In addition, all microemulsions were stable for at least three months at 30 ± 1°C.     

Elaboration and properties of renewable polyurethanes based on natural rubber and biodegradable poly(butylene succinate) soft segments

Natural rubber (NR) is a renewable bio‐based polymer, while poly(butylene succinate) (PBS) belongs to the family of biodegradable renewable polymers. In this article, novel polyurethanes (PUs) were prepared using hydroxyl telechelic natural rubber (HTNR) and hydroxyl telechelic poly(butylene succinate) (HTPBS) as soft segments, and using toluene‐2,4‐diisocyanate (TDI) and 1,4‐butanediol (BDO) as hard segment. HTPBS oligomers of = 2000 and 3500 g mol^?1 were synthesized by bulk polycondensation of succinic acid (SA) with BDO. The polyurethane materials were obtained by casting process after solvent evaporation. The influence of the hard segment content and the molecular weight of HTPBS on the materials’ thermo‐mechanical properties were investigated by means of tensile testing, DSC, TGA, and DMTA. The obtained polyurethanes were amorphous with phase separations between hard and soft segments as well as between HTNR and HTPBS segments, and they exhibited good physical properties. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42943.     

Mechanical characteristics and thermal behaviours of polylactide blend films: influence of nucleating agent and poly(butylenes adipate-co-terephthalate)

Polylactide (PLA) blend films with poly(butylenes adipate-co-terephthalate) (PBAT) and a nucleating agent were prepared by the melt compounding technique. Thermal stability of the PLA decreased with added nucleating agent; in contrast, the decomposition temperature increased with the presence of PBAT. In addition, the differential scanning calorimetry thermograms demonstrated that the heterogeneous nucleation and cold crystallisation processes of the PLA blend films were accelerated.

The influence of the type and level of the nucleating agent and the presence of PBAT on the tensile properties, impact resistance, thermal stability and non-isothermal crystallisation behaviours of the PLA blend films were investigated. Both the PLA/nucleating agents and the PLA/PBAT/nucleating agent blends showed significant effects from the changes in the nucleation process on their tensile properties, impact toughness and thermal behaviour. Furthermore, the impact energy that the PLA blends absorbed during the entire impact tension test was obviously enhanced by the increased content of the nucleating agent.     

Electrospun Methacrylate-Based Copolymer/Indomethacin Fibers and Their Release Characteristics of Indomethacin

Three methacrylate-based copolymers [i.e., poly(methacrylic acid-co-methyl methacrylate) (E-L100), poly(ethyl acrylate-co-methyl methacrylate-co-trimethyl-ammonioethyl methacrylate chloride) (E-RLPO), and poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate) (E-EPO)] were successfully electrospun into fibers, using ethanol (EtOH) as the spinning solvent. However, electrospinning of these methacrylate-based copolymers and indomethacin (10% by weight of the copolymer) was only successful when an equivolume of EtOH and ethylacetate (EA) was used as the co-solvent system. The drug-loaded as-spun copolymeric fibers appeared to be flat, with the size ranging between 1.2 and 2.5 μm. At 24 h, the amount of the drug released from these drug-loaded as-spun copolymer fibers was about 55%, 30%, and 18% for drug-loaded as-spun E-EPO, E-L100, and E-RLPO fibers, respectively.