FORMULATION DEVELOPMENT AND EVALUATION OF ALLOPURINOL SOLID DISPERSIONS BY SOLVENT EVAPORATION TECHNIQUE

Objective: The main objective of the research work is to develop and characterize allopurinol (ALPN) solid dispersions with different polymers to enhance solubility, enrich dissolution profile and improve patient compliance.Methods: ALPN solid dispersions were prepared by solvent evaporation technique using various grades of polyethelene glycol (PEG) such as PEG 4000 and PEG 6000 with different ratios like 1:0.5, 1:1, 1:1.5 and 1:2 and after formation of solid dispersions all physicochemical properties were examined.Results: All the formulations were found within the permissible pharmacopoeial limits for various physicochemical parameters. The pre-formulation studies, like Fourier, transform infrared spectroscopy (FTIR) showed the absence of drug-excipient interactions. The solubility and dissolution profiles of the sample were increased with increasing the concentration of ALPN solid dispersions. Solvent evaporation was proved to be a successful technique for the development of stable solid dispersion of ALPN. The dissolution amount percentage of ALPN formulations was found between 39.58±2.5 to 94.95±1.8 % within 60 min.Conclusion: Hence, from the all evaluation studies, it was evident that F1 formulation was the better formulation. F1 formulation (ALPN: PEG 4000 in the ratio of 1:0.5), 94.95±1.8 % drug released within 50 min.

Pattern of Constipation and Response to Polyethylene Glycol in Children

Introduction: Constipation is a common problem in children with worldwide prevalence between 0.7% and 29.6%.Materials and Methods: Total number of children was 232 out of which 16 were discarded due to loss in follow up. Inclusion criteria: Any child aged one month to ten years presenting with constipation. We used NASPGHAN definition of constipation. Exclusion criteria: Critically sick and hemodynamically unstable patients were excluded from the study. Data were collected for age, sex, duration of constipation, symptoms and signs such as stool frequency, stool consistency, pain during defecation, presence of blood in stool, fecal and urinary incontinence, and presence of fecal impaction or an abdominal mass. Clinical evaluation (history and physical examination) of all patients was done by the same physician to avoid bias in clinical finding. Polyethylene glycol (PEG) was tried in all patients in a dose of 0.3 to 2.1g/kg. Response was defined as passage of at least one semisolid stool without discomfort with use of PEG for at least 4 weeks.Results: In our prospective study done on 232 patients with constipation over three year period (dividing patient’s into1month to 5months, 6months to 5year and 6 years to 10 years) revealed that constipation is mostly prevalent in 6 months to 5 year age group with slight male preponderance. Most of them had symptom onset after six months of age. Commonest symptom was hard stool in general (79.6%) but prevalence of pain abdomen increases with age and peaks in above five year group. Commonest sign is palpable fecal mass. Complications-urinary dysfunction, fecal incontinence, fissure are common in older age group. Functional constipation was the commonest cause (96.2%). Hirschprung disease was diagnosed in 1.4%. Polyethylene glycol shows good response in above 6 months of age groups.Conclusion: Functional constipationis the commonest cause of constipation. Mostly affected group is six months to five years. Polyethelene Glycol is an effective treatment especially after six months. J Nepal Paediatr Soc 2016;36(3):263-267.

Anti-Pegaspargase, Anti-Calaspargase Pegol , and Anti-Polyethelene Glycol Antibody Incidence in High Risk Acute Lymphoblastic Leukemia Patients Receiving Pegaspargase or Calaspargase Pegol and Associated Anaphylactic or Hypersensitivity Reaction Rates: Results from Children's Oncology Group (COG) Study AALL07P4

Introduction Asparaginase is a critical component in the treatment of acute lymphoblastic leukemia (ALL). COG AALL07P4 evaluated the pharmacokinetic (PK) and pharmacodynamic comparability of pegaspargase (ASP) and calaspargase pegol (CASP) as part of an augmented BFM chemotherapy regimen for the treatment of newly-diagnosed, NCI high-risk, B-precursor ALL (Angiolillo, JCO 2014). Both ASP and CASP consist of E. coli L-asparaginase linked to polyethelene glycol (PEG) utilizing a succinimidyl succinate or succinimidyl carbamate linker, respectively. Antibodies to either asparaginase or PEG have been associated with rapid clearance of asparaginase. Methods Of the 166 patients randomized, 1 was inevaluable; 54 patients were randomized to ASP at 2500 IU/m2,43 to CASP at 2500 IU/m2 and 69 toCASP at 2100 IU/m2; both CASP treatment groups were pooled for this report. Blinded analyses of anti-ASP and anti-CASP antibodies were performed on samples obtained prior to asparaginase administration and at protocol specified time-points through the second cycle of maintenance therapy inpatients withadequatesamples (50 and 111 patients in the ASP and CASP treatment groups, respectively). Immunogenicity assessment included the detection of binding anti-ASP or anti-CASP antibodies by a validated direct enzyme-linked immunosorbent assay (ELISA). All detected antibodies were analyzed in a neutralizing anti-ASP/anti-CASP antibody assay for their neutralizing capacity using a validated enzymatic coupled activity assay. Analysis of anti-PEG antibodies using ELISA was assessed retrospectively, in a subset of patients who had available specimens, as this had not been part of the initial trial design, in 26 and 42 patients in the ASP and CASP treatment groups, respectively, including all patients with anti-ASP/anti-CASP antibody positive samples. All grades of anaphylactic reactions and hypersensitivity were reported according to the CTCAE v3.0 prior to July 2011 and converted into v4.0 codes with subsequent AEs collected in v4.0 beginning with the first asparaginase dose until 60 days after the last dose of asparaginase or being switched to erwinia asparaginase. Results Our analysis of anti-ASP and anti-CASP antibodies showed fewer anti-CASP antibodies: 3.6% (4 /111 patients) than anti-ASP antibodies: 10.0% (5/50 patients). The majority of positive post treatment antibodies were transient and not detectable at subsequent visits. Three patients (one in the CASP and two in the ASP treatment group) showed positive results for binding antibodies at the last tested time point; it is unknown whether these antibodies are of transient or persistent nature. Among 111 patients treated with CASP, 29 (26.1%) developed an anaphylactic and/or hypersensitivity reaction and 2 of these (6.9%) had anti-CASP present at the time of reaction; among 50 patients treated with ASP, 14 (28%) developed an anaphylactic and/or hypersensitivity reaction and 2 of these (14.3%) had anti-ASP present at the time of reaction. Only one patient in the CASP treatment group tested positive for neutralizing antibodies at one time point with negative results at subsequent time points. Focusing on the subset of patients who had available anti-PEG antibody data, we found that 6/46 (13%) in the CASP treatment group had detectable anti-PEG antibodies as compared to the 5/26 (19.2%) in the ASP treatment group. In the patients who had anaphylactic and hypersensitivity reactions, 2/10 (20%) patients treated with CASP had either anti-CASP or anti-PEG antibodies, as compared to 5/8 (62.5%) patients treated with ASP who had either anti-ASP or anti-PEG antibodies. Observed differences in antibody responses were not statistically significant. As we previously reported, many patients with clinical anaphylactic and hypersensitivity reactions did not have antibodies detected. Conclusions In this preliminary analysis of COG AALL07P4, patients receiving CASP have numerically less antibody formation to both asparaginase and PEG than patients receiving ASP. Fewer patients with anaphylactic and hypersensitivity reactions to CASP had detectable antibodies as compared to those who received ASP. Since these antibodies may be associated with rapid clearance of asparaginase, further evaluation of PK and immunogenicity is ongoing. Additional investigation is warranted to better understand the clinical significance of these findings. Table Table. Disclosures Schore: Onyx/Amgen: Research Funding; Millennium Pharmaceuticals, Inc: Research Funding; Baxalta: Honoraria; Merck: Research Funding. Bleyer:Jazz Pharmaceuticals: Honoraria, Speakers Bureau. Lebedinsky:Shire: Employment. Zhang:Shire: Employment. Koppensteiner:Shire: Employment. Loh:Abbvie: Research Funding; Briston Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Hunger:Erytech: Honoraria; Patent: Patents & Royalties: Dr. Hunger is a co-inventor of a patent (#8658,964) for the identification of novel subgroups in high risk B-ALL and outcome correlations and diagnostic methods related to the same; Spectrum Pharmaceuticals: Honoraria; Sigma Tau Pharmaceuticals: Honoraria; Jazz Pharmaceuticals: Honoraria; Merck: Equity Ownership; Pfizer: Equity Ownership; Amgen: Equity Ownership.

Partial Purification and Characterisation of Alcohol Dehydrogenase from Acetobacter aceti Isolated from Palm Wine

Palm wine is a very important alcoholic beverage whose consumption is limited because it spoils easily. The study was designed to isolate Acetobacter aceti from palm wine, then extract, purify and characterize alcohol dehydrogenase (AD) from the A. aceti. Muller Hilton agar was used as medium for the growth of A. aceti for 48 h. The cells were harvested and subjected to ultrasonication using 500 watt ultrasonicator. Enzyme assay was carried out in both the supernatant and pellet. The enzyme was precipitated by polyethelene glycol 6000 while gel filtration was used for purifying the enzyme. The effects of pH, temperature and substrate concentration on AD were evaluated. The isolated A. aceti was gram negative, rod shaped, catalase positive, oxidase negative and was able to oxidize acetic acid to CO2 and H2O. Triton X-100 (0.3%) was the most effective concentration in solubilizing the protein (AD), while 15% polyethelene glycol 6000 was the most effective concentration for the precipitation of AD. An optimal pH of 5 was obtained with an optimal temperature of 50 °C. The most appropriate to solubilize and precipitate AD were 0.3% triton X-100 and 15% polyethelene glycol 6000 respectively, while AD activity was reduced under acidic pH, as well as for low and high temperatures.

The Effect of Oxygen Precursor Concentration to the Iron Oxide Nanoparticles Properties for Lateral Flow Immunoassay Application

In this study, the influence of hydrogen peroxide (H2O2) concentration to the iron oxide nanoparticles (IONPs) properties prepared using the precipitation method was investigated. The H2O2concentration was varied from 0.85 M to 5.1 M. The concentration of H2O2influenced the crystallinity and the growth rate of the IONPs precipitates. Increasing the concentration of H2O2increased the crystallinity and expedited the growth rate of IONPs. The optimum concentration of H2O2was 1.7 M. From the transmission electron microscopy (TEM) images, the size of IONPs obtained was ~14 nm and the X-ray diffraction (XRD) spectra showed the presence of spinel cubic lattice of maghemite (γ-Fe2O3). The magnetic measurement of IONPs using vibrating sample magnetometer (VSM) was showed that the IONPs exhibited superparamagnetic properties. Furthermore, the electrostatic repulsion using percloric acid (HClO4) and steric stabilization using silane polyethelene glycol (SiPEG) were created surround IONPs in order to obtain a stable colloidal IONPs for the conjugation process. The stable IONPs were then conjugated to the antibody and tested in the lateral flow immunoassay as the labelling agent.

The Effect of Synthetic Silica on Ultrafiltration PSf Membrane

This study investigates the effects of synthetic silica(SiO2)with different weight percentage concentrations on the morphology and performance of the polysulfone (PSf) and polyethelene glycol (PEG) based membrane ultrafiltration (UF). Phase inversion method was used to prepare PSf/PEG ultrafiltration (UF) flatsheet membrane. SiO2 and N-Methyl 2 Pyrrolidone (NMP) were used as an additive and solvent respectively. The fabricated membrane was characterized by scanning electron microscope (SEM), X-ray diffraction (XRD) and the performances of the membranes were measured in term of pure water flux by using distilled water and solute rejection at different wastewater concentration at 50%, 75% and 87.5%. The result showed that the addition of 2% silica in the dope solution increased the permeation in terms pure water flux and the best rejection with 62 Lm-2 h-1 and 89% (at 87.5 % waste water dilution) respectively

The Effect of Polyethelene Glycol on The Performance of Polysulfone Membrane Blend with Silica From Rice Husk

In the present work, the effect of rice husk silica (RHS) on the performance of polysulfone (PSf) blended with polyethylene glycol (PEG) membranes were investigated. The hybrid ultrafiltration membranes were prepared by phase inversion technique. The membrane performance was analyzed by using pure water flux, humic acid for the rejection test and followed by the membrane characterization. Results showed that PEG increased membrane pure water flux to 621.212 LMH and rejection humic acid at and 98%. The analysis of SEM revealed that PEG obviously changed the microstructure of the membrane especially at the top and sub layer.

Iron Salt Concentration Effect to the Precipitation of Iron Oxide Nanoparticles Conjugated Antibody

This study covers the effect of ferrous chloride (FeCl2) concentration on the formation of iron oxide nanoparticles (IONPs) via the precipitation method. IONPs with appropriate surface functionalization were synthesized in order to obtain a stable colloidal IONPs (ferrofluid) for the conjugation process. The electrostatic repulsion using percloric acid (HClO4) and steric stabilization using silane polyethelene glycol (SiPEG) were generated. The optimum concentration of FeCl2was at 0.3 M. From the transmission electron microscopy (TEM) image, the size of IONPs obtained was ~13 nm. The stable IONPs were then conjugated to the antibody and tested in the lateral flow immunoassay as the labelling agent. The conjugated IONPS with the antibody was proven sensitive to the Brugian Filiarisis disease.