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Biomedical subjects

N Farah

Publications and source records attributed to N Farah.

14 recordsLinked to original sources
PubMed2002

Developing a study method for producing 400 microm spheroids.

The aim of this work was to obtain 400 microm spheroids that can be sprinkled on food to improve patient compliance particularly in the case of children and old people. A methodology to select wet masses for extrusion-spheronization through a 400 microm orifice was developed. The first step was to define the parameters that make it possible to assess the qualities required by the wet mass and the extrudates and evaluation norms: plasticity, cohesiveness, brittleness of the mass and the extrudates, and appearance of extrudates. A feasibility assay was then performed on the cylinder extruder, showing that extrusion of the lactose/Avicel PH 101/water (50/50/60) mass is not feasible through the 400 microm orifice. Precirol ato 5 and Gelucire 50/02 wetted with a sodium lauryl sulfate solution at 0.5% show plastic flow through the 400 microm diameter orifice. The presence of Avicel PH 101 does not improve plasticity for this orifice. Micropellets of 400 microm have been proved feasible as long as excipients with suitable pharmaceutical technological properties are used. After proving the feasibility of 400 microm spheroids of Gelucire 50/02, we considered the association of a drug with it.

Cellulose↗
PubMed2000

Hot-melt coating technology. I. Influence of Compritol 888 Ato and granule size on theophylline release.

The aim of this work was to study the influence of theophylline granule size and the percentage of Compritol 888 Ato on in vitro drug release from granules and tablets. The granules were coated in a fluidized bed apparatus. The dissolution profiles of these granules differed from those of granules coated with classical agents, and there were also differences between the various sieve fractions studied. Drug release was characterized by a rapid-release phase, followed by a slow-release phase. Results indicate that theophylline release can be controlled by controlling granule size. Inspection of the appearance of the tablets at the end of the dissolution test revealed that all tablets containing Compritol 888 Ato remained intact. This indicated that the Compritol 888 Ato used in the tablet formulation created an inert matrix through which the drug diffused. It was found that the Higuchi relationship of linear square root of time was the best model to describe the release kinetics of the drug from tablets. This also confirmed that a matrix diffusion-controlled mechanism was operative. Given the difference between the dissolution profiles of the granules and the tablets, it was concluded that this matrix is formed during compression.

Bronchodilator Agents↗
PubMed2000

Cisplatin DNA adduct detection and depurination measured by 32P DNA radiolabeling and two-dimensional thin-layer chromatography: a time and concentration study.

Platinum-based chemotherapies cause the formation of DNA adducts and have profound effects on DNA. This study measured cis-diamminedichloroplatinum II (cisplatin) DNA adducts by 32P-radiolabeling DNA, enzymatically digesting radiolabeled DNA, separating the formed adducts on two-dimensional thin-layer chromatography, and quantitating the adducts with autoradiography and densitometry. HeLa DNA was incubated with cisplatin at varying concentrations (6.25-325 nM) and times (0 min to 72 hr). Cisplatin rapidly depurinated dGMP and dAMP (90%, 15-min incubation with 325 nM cisplatin). Partial depurination of dGMP (15%) and dAMP (25%) occurred with lower cisplatin concentrations at equal incubation times. A minimum of four new adducts, with relatively rapid migratory patterns, were detected at high cisplatin concentrations with short incubation times. These results indicate that the depurination of DNA correlates with DNA adduct formation and that the quantification of these adducts may be applicable to monitoring tumor and host cell response to cisplatin chemotherapy.

Adenosine Monophosphate↗
PubMed2000

Hot melt coating technology: influence of Compritol 888 Ato and granule size on chloroquine release.

The tangential spray technique was used to coat chloroquine granules with Compritol 888 Ato in a fluidized bed (Glatt GPCG-1,1). After validation of the assay method for chloroquine, dissolution tests were carried out on four size fractions obtained from the same batch of granules. The dissolution profiles obtained showed differences in the rate of release between one fraction and another, despite the fact that each of these fractions had been coated with the same quantity of wax. This suggests that the rate of release of the chloroquine may be adjusted by controlling the size of the granules. Furthermore these dissolution profiles were characterized by a rapid release phase followed by a slow release phase. Examination of the surfaces of the granules from the various size fractions under a scanning electron microscope revealed that Compritol did not form a continuous film but existed rather as a lipid environment around the granule. This lipid environment was made up of solidified droplets of the wax which had become piled up on the surface of the granule. Compression of the granules produced tablets which remained intact until chloroquine dissolution was complete. This undicated that the active substance diffused across the Compritol matrix generated during compression. Determination of the dissolution kinetics using the Higuchi model demonstrated the diffusion release mechanism.

Amebicides↗
PubMed1999

Compritol 888 ATO: an innovative hot-melt coating agent for prolonged-release drug formulations.

The aim of the present study was to assess the coating of drug-loaded sugar beads and lactose granules with Compritol 888 (National Formulary (NF)--Glyceryl Behenate). Theophylline was used as tracer and layered onto the beads, or granulated with lactose and sugar. Coating conditions (temperature, spray-rate, air pressure, etc.) were investigated for the production of prolonged release beads or granules, and dissolution kinetic curves were discussed. The study confirms the satisfactory coating potential of the hot-melt fluid-bed coating process on large spherules or granules. The optimized conditions confirm previous work, underscoring the considerable importance of the temperature of molten coating materials and the atomization air pressures. More sophisticated equipment would undoubtedly produce more efficient coating but the technique nevertheless seems promising. Practical data is now available for standard top spray equipment for fine and coarse granules. (1) Granule and spherule surface adhesion is controlled and consistent; (2) the coating is homogeneous, with continuous atomization and spraying onto the support; and (3) the release profile is directly related to the quantity of wax applied. Several competing mechanisms are also involved, including a diffusion-controlled process and a dissolution mechanism. Dissolution profiles appear to be consistent from one batch to another.

Air Pressure↗
PubMed1997

In vivo determination of 5-bromo-2'-deoxyuridine incorporation into DNA tumor tissue by a new 32P-postlabelling thin-layer chromatographic method.

The halopyrimidine 5-bromo-2'-deoxyuridine (BUDR) can serve as one of many indicators of tumor malignity, complementary to histologic grade. We have developed a thin-layer chromatographic (TLC) technique that can assess tumor DNA base composition and analogue (BUDR) incorporation which vies with immunochemistry for BUDR. This requires post-labeling DNA by nick-translation and radioactive 5'-phosphorylation of representative 32P-alpha-dNMPs (deoxynucleotide monophosphates). Subsequent 3'-monophosphate digest exchanges a radioactive 32PO4 for the neighboring cold nucleotide. Separation in two dimensional PEI-cellulose TLC is carried out in acetic acid, (NH4)2SO4, and (NH4)HSO4. TLC of dNMPs was applied to control HeLa DNA, and HeLa cells receiving BUDR. BUDR is detected in 10(6) HeLa cells after 12-72 h incubations. Findings in HeLa DNA demonstrate normal TLC retention factors for all 32P-dNMPs. Two dimensional R(F) (x,y axes in cm) demonstrate: dAMP=1.4, 9.4; dCMP=10.0, 13.5; dGMP=4.6, 4.4; dTMP=9.0, 7.4; and BUDRMP 6.4, 6.6. This technique quantifies BUDR--which parallels tumor S phase, and serves as an indicator of labelling index (LI).

Bromodeoxyuridine↗
PubMed1997

Retrograde treatment of ureteropelvic junction obstruction using the ureteral cutting balloon catheter.

PURPOSE: We assessed the efficacy and safety of a new cutting balloon catheter to treat symptomatic ureteropelvic junction obstruction in adults. MATERIALS AND METHODS: A total of 32 adults (mean age 40 years, range 18 to 79) underwent retrograde balloon incision for symptomatic ureteropelvic junction obstruction (27 primary and 5 secondary cases). Treatment outcome was based on improvement of symptoms and resolution of obstruction by excretory urography or diuretic renal scintigraphy. RESULTS: A total of 36 retrograde endopyelotomies was performed on 32 patients. Of 4 patients who underwent repeat endopyelotomy 2 had resolution of persistent obstruction. At a mean followup of 14 months (range 3 to 28) 28 of 32 patients (87.5%) were rendered symptom-free and had no obstruction on excretory urography or diuretic renography. Average hospital stay was 1.8 days (range 0 to 6) and the complication rate was 15.6% (postoperative bleeding, fever and ileus). Treatment failed in 4 patients and subsequent open pyeloplasty was successful. CONCLUSIONS: Retrograde balloon incision endopyelotomy appears to be a safe and effective treatment for ureteropelvic junction obstruction.

Adolescent↗
PubMed1993

Comparison of nephrostomy drainage systems.

Forty patients undergoing nephrostomy insertion were randomised into 2 groups: those maintained on intermittently closed and those on permanently closed drainage systems. The average cost of managing a patient in the former group was one-eighth that of the latter and was not associated with any increase in morbidity.

Costs and Cost Analysis↗
PubMed1992

Synthesis of cell-impermeable Cl-sensitive fluorescent indicators with improved sensitivity and optical properties.

Quinolinium compounds have been used as Cl-sensitive fluorescent indicators in cells and cell-free membrane fractions. To improve Cl sensitivity and for conjugation via nucleophilic reaction, the compounds 6-methoxy-N-(n-aminoalkyl)quinolinium bromide hydrochloride (AAQ) with alkyl chain lengths (n) of 2 (AEQ), 3 (APQ), and 4 (ABQ) were synthesized. AAQ was water soluble, fluorescent, and quenched by Cl. The Stern-Volmer constants (KCl) for quenching of protonated AEQ, APQ and ABQ by Cl were 354, 322, and 272 M-1, respectively, higher than KCl for 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ; 118 M-1). To eliminate pH-dependent fluorescence, 6-methoxy-N-(3-trimethylammoniumpropyl)quinolinium dibromide (TMAPQ) was synthesized (KCl, 310 M-1). To red shift fluorescence excitation and emission spectra, 6-phenyl-N-(3-trimethylammoniumpropyl)quinolinium dibromide (phenyl-TMAPQ) (emission 475 nm) and N-(3-trimethylammoniumpropyl)phenanthridinium dibromide (TMAPP) (excitation 380 nm) were synthesized. AEQ and ABQ were conjugated with neutral dextran activated by cyanogen bromide to give indicator-to-dextran mole ratios of 5 to 20. KCl values at pH 7.4 were 132 (AEQ-dextran) and 237 M-1 (ABQ-dextran). To construct a single molecule with Cl-sensitive and insensitive moieties, the bichromophores 6-methoxy-N-(n- dansylsulfonamidoalkyl)quinolinium with alkyl chains of two and four were synthesized. The new Cl-sensitive indicators were used for measurement of intracellular Cl activity and for the labeling of endocytic vesicles in 3T3 fibroblasts and T84 cells. Our results indicate that N-substitution of quinoline with positively charged moieties gives increased Cl sensitivity, and extension of ring conjugation gives indicators with red-shifted fluorescence spectra.

Cell Membrane Permeability↗
PubMed1989

New combination chemotherapy programme for bladder cancer.

Forty patients with either metastatic, post-radiotherapy recurrent, or poor prognosis locally advanced transitional cell carcinoma of the bladder were treated in a new combination chemotherapy programme with methotrexate, vinblastine, mitozantrone and JM8 (carboplatin); 33 patients were assessable for response. There were 9 complete responses (27%), 12 partial responses (36%) and 7 disease stabilizations (21%); 5 patients (15%) had progressive disease. The median duration of complete response has not been reached and is in excess of 9 months (range 4- greater than 18 months). This regimen was without significant toxicity and this is in contrast with M-VAC, which is thought to be currently the most effective treatment for urothelial cancer.

Adult↗
PubMed1989

Two-monthly depot gonadotropin releasing hormone agonist (buserelin) for treatment of prostatic cancer.

The agonist analogues of gonadotropin-releasing hormone provide an alternate medical therapy for prostatic cancer. Current methods of administration of these analogues by daily injection or nasal spray is sub-optimal in an elderly population. We have performed a pharmacological and endocrine evaluation of a new depot preparation of one such analogue, buserelin, active for 2 months. Thirty patients with advanced symptomatic prostatic cancer were treated. Serum testosterone was suppressed for the duration of treatment which ranged up to 14 months. The release characteristics of the depot were consistent and showed minimal variation between patients. This 2-month preparation of buserelin offers and advantage to the patient with prostatic cancer, over current treatment regimens.

Adult↗
PubMed1988

Dry adsorbed emulsions: an oral sustained drug delivery system.

The oral sustained drug delivery system "dry adsorbed emulsion" was defined as an organized dispersion of hydrophilic and hydrophobic particles whose structure was initiated by the structure of a water-in-oil (W/O) emulsion. Sodium salicylate was dissolved in the aqueous phase of the primary W/O emulsion as an active drug. The aqueous phase of the W/O emulsion was adsorbed by a hydrophilic silica and then a hydrophobic silica was added to the preparation to obtain a stable and solid pulverulent form. The physicochemical structure of a "dry adsorbed emulsion" was described and observed by electron microscopy. The effect of different oils, castor oil and a silicone oil, on the sustained drug release was studied at two different pH values, 1.2 and 7.4, to simulate the gastric and intestinal medium, respectively. The properties of these forms were retained for more than one year at room temperature storage.

Adsorption↗
PubMed1988

The clinical and endocrine assessment of three different antiandrogen regimens combined with a very long-acting gonadotrophin-releasing hormone analogue.

Tumor flare is reported in up to 40% of patients treated with gonadotrophin-releasing hormone analogues for prostate cancer. In order to investigate the optimal way to eliminate tumor flare, we have treated patients with one of three different antiandrogen regimens used in combination with gonadotrophin-releasing hormone (GnRH) agonist. The early results of this study are presented here. Thirty patients with advanced symptomatic disease were randomized to receive either cyproterone acetate 50 or 100 mg three times daily or flutamide 250 mg three times daily given for 1 week before and during the first month of GnRH agonist treatment. The endocrine profiles of these patients were compared with those of historic controls treated with depot agonist alone. Three patients treated with low-dose cyproterone acetate and one with flutamide developed a transient exacerbation of their disease. No patients treated with the higher-dose cyproterone acetate regimen developed tumor flare. No patients treated with cyproterone acetate had an increase in serum testosterone above baseline following depot GnRH agonist implantation. All patients treated with flutamide had increases in serum testosterone, but this did not significantly increase further with implantation. This study suggests that all patients receiving GnRH agonist treatment should be pretreated with cyproterone acetate 100 mg three times daily for 1 week before implantation and for the first treatment month.

Aged↗