Biodegradable poly(D,L-lactic acid) (PLA) microspheres containing hexamethylmelamine (HMM) were developed for potential use in chemoembolization and intraperitoneal implantation. The emulsion-solvent-evaporation/extraction method was used to prepare 15 formulations with different drug/polymer ratios, solvent compositions and emulsifer concentrations in the continuous aqueous phase. A central composite experimental design was used, with five levels of the three different factors. All formulations resulted in the formation of discrete matrix microspheres containing crystalline drug. The mean particle sizes of the microsphere formulations ranged from 62-348 microm and the effect of the independent variables on microsphere size was satisfactorily predicted using response surface methodology. For theoretical drug loads of 5-40%, efficiency of entrapment ranged from 75-107% and porosities of the microspheres were between 0-6.5%. The rate of drug release from the microspheres depended on drug loading and particle size. Microspheres with 22.5% or greater theoretical drug content released drug rapidly, with almost complete release occurring in 70 h or less. Formulations with drug loading of 5% and 9.57%, however, released drug very slowly, with less than 50% released in 40 days. Release kinetics of narrow sieve cuts of microspheres with high drug load (35.4%) followed square root of time profiles.

Altretamine↗

PubMedDate not supplied

Metabolism of intranasally applied cocaine.

Surprisingly little is known about the metabolism and toxicity of cocaine in man. In this study serum obtained following nasal surgery was assayed for benzoylecgonine (the major metabolite of cocaine) by radioimmunoassay. It was found that cocaine was rapidly hydrolyzed in the serum. Benzoylecgonine was detectable in the serum at 15 minutes. The peak blood level of the metabolite appeared at 4.5 hours with a peak concentrations of 872.9 ng/ml. The half time clearance of the metabolite from the serum was 5.5 hours. A discussion of variables which must be considered in deriving, by a scientific method, a maximum safe clinical dose is presented.

Administration, Intranasal↗

PubMedDate not supplied

Hypocalcemia following pharyngoesophageal ablation and gastric pull-up reconstruction: pathophysiology and management.

Profound hypocalcemia has been observed following surgical ablation of malignancies in the hypopharynx, larynx, cervical trachea, and esophagus. Adequate control of these tumors may require extirpation of the visceral compartment of the neck and upper mediastinum. Preservation of parathyroid glands is sometimes inconsistent with good oncologic principles. Postoperative hypocalcemia develops rapidly, and high-dose intravenous calcium supplementation is required. Clinical observations indicated that requirements for calcium supplementation were reduced dramatically once oral feeding was instituted. It is postulated that dysfunction arising from surgical manipulation of the duodenum, the primary site for active calcium absorption, and bypass of that bowel segment by the feeding jejunostomy are primary contributors to the severity of hypocalcemia. A plan of management is proposed that includes early postoperative administration of 1,25-dihydroxyvitamin D or dihydrotachysterol, active vitamin D metabolites that promote the absorption of calcium. Early oral feeding is encouraged. Other mechanisms of calcium loss, appropriate calcium management, and parathyroid autotransplantation are discussed.

Adult↗

PubMedDate not supplied

Recurrent adenoid cystic carcinoma of the trachea: intraluminal radiotherapy.

Malignant neoplasms of the trachea are rare lesions, of which adenoid cystic carcinoma constitutes 30%. A case of extensive tumor recurrent after primary radiotherapy is presented. Surgical resection and radioisotope implantation were impossible. A method was devised for placement of intraluminal iridium 192 by casting six small hollow plastic tubes to the outer circumference of a Silastic endotracheal tube. This was an easy, safe, and effective method of delivering radiation to the trachea while sparing other vital structures and organs. Excellent tumor response and palliation were achieved. The literature is reviewed and the problems in diagnosis of this tumor are discussed. A comprehensive plan for early diagnosis is presented. All current methods of treatment are discussed, and the need for aggressive surgical management is stressed.

Adenoids↗

PubMedDate not supplied

The midline vertical forehead flap.

The midline vertical forehead flap is an unheralded flap that has valuable and specific application. It is ideal for certain reconstructions around the nose, orbit, and upper melonasal regions. The color match is excellent. The donor area is repaired per primum and because there is a double blood supply it rarely fails when nondelayed and rotated 180 degrees.

Cheek↗

PubMedDate not supplied

Poly(hydroxybutyrate-hydroxyvalerate) microspheres containing progesterone: preparation, morphology and release properties.

The biodegradable polyesters, poly(hydroxybutyrate) (PHB) and poly(hydroxybutyrate-hydroxyvalerate) (PHBV) were investigated for use as sustained delivery carriers of a model drug, progesterone. Spherical microspheres containing the drug were prepared by an emulsion solvent-evaporation method with gelatin as an emulsifier. Methylene chloride as the polymer solvent yielded smoother microspheres than chloroform. The surface texture was also dependent upon the temperature of the preparation and polymer used. Surface crystals were observed when the drug loading was increased beyond 5 per cent w/w. Thermograms of the microspheres did not show an endotherm corresponding to the melting of the drug because the drug dissolved in the melted polymer while heating. The amount of residual solvent in the microspheres (gas chromatographic assay) ranged from 3.4 to 58.4 ppm and was dependent on the processing temperature, concentration of the polymer in the solvent and the polymer composition. In vitro release of the drug was slowest from microspheres made from copolymer containing 9 per cent hydroxyvalerate. A less porous microsphere matrix was formed by this copolymer.

Calorimetry, Differential Scanning↗

PubMedDate not supplied

Formulation, preparation and dissolution characteristics of propranolol hydrochloride microspheres.

Propranolol HCl was encapsulated with cellulose acetate butyrate (CAB) by an emulsion-solvent evaporation method to obtain discrete, spherical microspheres. The effects of drug to polymer ratio and microsphere size on dissolution characteristics were studied. Drug release was faster in simulated intestinal fluid than in simulated gastric fluid. Unencapsulated propranolol HCl powder had very rapid dissolution, as expected. Release rate from CAB microspheres increased with higher drug to polymer ratios and decreased with increasing diameter. Drug release from microspheres sizes larger than 180 microns was reasonably well described by the spherical matrix model. For microsphere size fractions between 127 and 359 microns the relationship between the 50 per cent release time and the square of the microsphere diameter was linear (r = 0.9999).

Cellulose↗

PubMedDate not supplied

Effect of compression pressure on physical properties and dissolution characteristics of disintegrating tablets of propranolol microspheres.

Propranolol HCl was encapsulated with cellulose acetate butyrate by an emulsion-solvent evaporation method. Three direct compression diluents were blended with appropriate size fractions of the microspheres and each formulation was compressed at several pressures to give tablets that readily disintegrated in water. Tablets with microcrystalline cellulose (MC) as the diluent had the highest tablet crushing strength at any given compression pressure. Heckel plots of all the microsphere-diluent blends were nonlinear, indicating that the consolidation may result from crushing and rearrangement of the individual particles in addition to plastic deformation. Tablet properties and estimated yield pressures showed that MC was the most suitable diluent for compression of propranolol HCl microspheres. Drug release from compressed tablets was always faster than from uncompressed microspheres, but useful sustained-release characteristics were retained. Dissolution tests of MC formulations of the tableted microspheres showed increased release rate constants and decreased 50 per cent dissolution times compared to microspheres that had not been compressed. This result indicated that rupture of some of the microspheres had occurred. The drug release rate increased at higher compression pressures due to the rupture of a greater proportion of microspheres. Larger changes in release rate and t50 percent were observed with larger microspheres sizes. Generally, the least compression pressure that gives tablets with acceptable properties is preferred.

Cellulose↗

PubMedDate not supplied

Chemical, dissolution stability and microscopic evaluation of suspensions of ibuprofen and sustained release ibuprofen-wax microspheres.

Chemical stability studies of suspensions of ibuprofen powder and ibuprofen-wax microspheres were performed using an accelerated stability protocol with a modified high performance liquid chromatography (HPLC) procedure. The variables considered were pH, suspending agents and temperature. The study showed little or no chemical degradation in the different suspending agents after storage for three months. Dissolution stability was examined in suspensions of ibuprofen microspheres made from an optimized formulation with 17% drug loading. The storage temperature were 23, 37 and 45 degrees C. Other variables for the dissolution stability studies were suspending agents, wax types, suspending medium pH and microsphere size. Suspensions of ceresine wax microspheres stored at 37 degrees C showed faster drug release than room temperature storage, but suspensions stored at 45 degrees C showed an opposite effect. Microspheres suspended in syrup and stored at 37 degrees C had faster dissolution rates than microspheres suspended in methylcellulose at the same temperature, possibly as a result of an interaction between the syrup and the microsphere constituents. Suspensions of microcrystalline wax microspheres had better dissolution stability than microspheres made from ceresine wax. Higher suspending medium pH resulted in faster release of drug from the suspended microspheres, but particle size did not significantly affect the dissolution stability.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMedDate not supplied

Development and characterization of buoyant theophylline microspheres with near zero order release kinetics.

The objective of this study was to prepare floating theophylline microspheres with zero order release profiles for use as buoyant reservoirs with increased retention time in the stomach. The microspheres were prepared by a modified emulsion-solvent evaporation method using a polymer mixture of cellulose acetate butyrate and Eudragit RL 100 (1:1). The drug-polymer dispersions were pressurized under carbon dioxide gas which dissolved in the drug-polymer dispersions and formed bubbles upon the release of the pressure. Some of the bubbles were entrapped in the dispersed drug-polymer droplets and eventually formed internal cavities in the microspheres. The resulting microspheres were characterized for size distribution, morphology, density, drug-polymer content, buoyant capacity and drug release behaviour. The microspheres were spherical with relatively smooth surfaces with round hollow cavities. The microspheres and low densities (less than 1 g/cm3) and remained floating for more than 24 h in pH 1.2 and 7.5 buffers. The dissolution profiles of the floating theophylline microspheres showed near zero order kinetics and sustained release in both pH 1.2 and 7.5 buffers. Modified microspheres processed with the addition of 2% w/v polysorbate 80 to the internal phase had smaller sizes, lower densities and faster drug release compared with those without the addition of the surfactant.

Cellulose↗