Phenylpropanolamine Research Articles

Influence of Eudragit® NE 30 D Blended with Eudragit® L 30 D-55 on the Release of Phenylpropanolamine Hydrochloride from Coated Pellets

The objective of this study was to investigate the influence of Eudragit® NE 30 D blended with Eudragit® L 30 D-55 on the release of phenylpropanolamine hydrochloride (PPA·HCl) from coated pellets. The miscibility of Eudragit NE 30 D/L 30 D-55 blends at different ratios was studied by using differential scanning calorimetry. The release of PPA·HCl from pellets coated with Eudragit NE 30 D alone and a Eudragit NE 30 D/L 30 D-55 blend, when stored at 40°C and 60°C, was determined by UV spectroscopy. Eudragit NE 30 D and Eudragit L 30 D-55 were miscible in ratios greater than 4:1. The curing time that was required to reach an equilibrium state decreased with the addition of Eudragit L 30 D-55. The presence of Eudragit L 30 D-55 also produced a film coating that was less tacky, and a dispersion of Eudragit NE 30 D containing Eudragit L 30 D-55 (5:1) was shown to prevent agglomeration of the pellets during coating and storage.

Treatment of urethral sphincter mechanism incompetence in 11 bitches with a sustainedrelease formulation of phenylpropanolamine hydrochloride

Between 1995 and 1999, urethral sphincter mechanism incompetence was diagnosed in 11 bitches. They had been treated with phenylpropanolamine hydrochloride at the recommended dose rate, but had shown no response...

Validation of a HPLC quantification of acetaminophen, phenylephrine and chlorpheniramine in pharmaceutical formulations: capsules and sachets

Acetaminophen, phenylephrine and chlorpheniramine are frequently associated in pharmaceutical formulations against the common cold. Their quantification presents several problems. A HPLC method for the simultaneous determination of these compounds in pharmaceutical formulations such as capsules and sachets, including the separation of impurities and excipients has been developed and validated. The selectivity of the method was also tested to be used if phenylpropanolamine hydrochloride were employed instead of phenylephrine. Final chromatographic conditions were a gradient elution, being solvent A: phosphate buffer 40 mM at pH 6.0 and solvent B: acetonitrile. At t=0, the mobile phase consisted of 92% A and 8% B and it changed with a linear gradient during 8 min to 75% A and 25% B. At min 8, it changed to 30% A and 70% B for 5 min and at t=15 min, it returns to the initial conditions (92% A and 8% B) during 1 min remaining at this composition until t=20 min. UV detection was performed at 215 nm for phenylephrine and chlorpheniramine, because at this wavelength sensitivity was higher than in other more characteristic wavelengths and it was necessary for the detection of minor compounds. For acetaminophen 280 nm was employed. Validation parameters permit to consider the method adequate.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules.

The release properties of phenylpropanolamine hydrochloride (PPA) from ethylcellulose (EC, ethylcellulose 10 cps (EC#10) and/or 100 cps (EC#100)) matrix granules prepared by the extrusion granulation method were examined. The release process could be divided into two parts, and was well analyzed by applying square-root time law and cube root law equations, respectively. The validity of the treatments was confirmed by the fitness of the simulation curve with the measured curve. At the initial stage, PPA was released from the gel layer of swollen EC in the matrix granules. At the second stage, the drug existing below the gel layer dissolved, and was released through the gel layer. Also, the time and release ratio at the connection point of the simulation curves was examined to determine the validity of the analysis. Comparing the release properties of PPA from the two types of EC matrix granules, EC#100 showed more effective sustained release than EC#10. On the other hand, changes in the release property of the EC#10 matrix granule were relatively more clear than that of the EC#100 matrix granule. Thus, it was supposed that EC#10 is more available for controlled and sustained release formulations than EC#100.

Properties of lipophilic matrix tablets containing phenylpropanolamine hydrochloride prepared by hot-melt extrusion

The objective of the present study was to investigate the influence of formulation factors on the physical properties of hot-melt extruded granules and compressed tablets containing wax as a thermal binder/retarding agent, and to compare the properties of granules and tablets with those prepared by a high-shear melt granulation (MG) method. Powder blends containing phenylpropanolamine hydrochloride, Precirol and various excipients were extruded in a single-screw extruder at open-end discharge conditions. The extrudates were then passed through a 14-mesh screen to form granules. The extrusion conditions and the optimum amount of wax to function as the thermal binder were dependent on the properties of the filler excipients. At the same wax level, drug release from tablets decreased in the order of using microcrystalline cellulose (MCC), lactose and Emcompress as the filler excipient. The observed differences in the dissolution properties of the tablets were due to the differences in the solubility, swellability and density of the filler excipients. Replacing Precirol with Sterotex K, a higher melting point wax, resulted in slightly increased dissolution rates, when the extrusion was performed at the same temperature conditions. Hot-melt extruded granules were observed to be less spherical than high-shear melt granules and showed lower values of bulk/tap densities. However, tablets containing MCC or lactose granules prepared by hot-melt extrusion (HME) exhibited higher hardness values. Slower drug release rates were found for tablets containing MCC by HME compared with MG. Analysis of the hot-melt extruded granules showed better drug content uniformity among granules of different size ranges compared with high-shear melt granules, resulting in a more reproducible drug release from the corresponding tablets.

Examination of oxidized cellulose as a macromolecular prodrug carrier: preparation and characterization of an oxidized cellulose-phenylpropanolamine conjugate

The purpose of this study was to investigate the use of 6-carboxycellulose (OC), a biocompatible and bioresorbable polymer, as a prodrug carrier for amine drugs. Phenylpropanolamine hydrochloride (PPA.HCl) was used as a model drug. OC and PPA were reacted in dimethylformamide (DMF) in the presence of 1,3-dicyclohexylcarbodiimide (DCC) for 2.5 days at room temperature. Filtration, followed by washing with methanol, and subsequent drying under vacuum, produced the conjugate in 65-78% yield. The amount of PPA in the product, determined from the difference in the carboxylic content before and after the reaction, was 24.2% (w/w), corresponding to a degree of substitution (DS) value of 0.7. The Fourier transform-infra red (FT-IR) spectrum of the conjugate, compared with that of OC and PPA.HCl, showed a new band at about 1533 cm(-1) attributable to a C = O (amide II) stretching and N single bond H (amide I and amide II) bending vibrations, a decrease in intensity of the characteristic free carboxylic acid carbonyl stretching band at about 1748 cm(-1), and a strong band at 1663 cm(-1) due to C = O (amide I) stretching vibration, suggesting that the OC is linked to PPA via an amide bond. The solid-state carbon-13 cross polarization/magic angle spinning nuclear magnetic resonance ((13)CCP/MAS NMR) spectrum of the conjugate was also consistent with this structure. The release studies performed in pH 4.5, 5.5, and 7.4 buffer solutions and in rat liver homogenate (pH 7.4), showed the conjugate to be more susceptible to hydrolysis at a lower pH and in the presence of rat liver homogenate. In conclusion, the results presented show that OC can be covalently linked to amine drugs via an amide bond in DMF using DCC as a coupling agent, and provide a macromolecular prodrug delivery system.

Analysis of multicomponent formulations containing phenylpropanolamine hydrochloride, caffeine and diazepam by using LC.

A reverse phase high performance liquid chromatography assay was carried out for the simultaneous determination of three active principles present in tablets of different origin and wide commercial use in the Province of Córdoba (Argentina). Prescriptions, commercially available as appetite suppressants, very often include the active principles Phenylpropanolamine Hydrochloride (I), Caffeine (II) and Diazepam (III). Simultaneous determination of these three drugs: anorexic, central nervous stimulant and tranquilizer, respectively, in pharmaceutical dosage forms has not been reported. In this study these active principles are quantified. The only sample preparation necessary for the analysis was their dilution with acetonitrile. The resulting solution was filtered and analyzed on a column packed with Supelcosil LC-18 (5 microm) with acetonitrile:water (30:70 v/v) as initial mobile phase (0.4 ml min(-1)) and the detection was performed at 254 nm. Then a linear gradient up to 100% acetonitrile in 18 min (3.0 ml min(-1)) was applied. The procedure was simple and suitable for quality control. The calibration function was established in the ranges of 0.072-0.168 mg ml(-1) for I, 0.036-0.084 mg ml(-1) for II and 0.06-0.196 mg ml(-1) for III. The detection limits of these compounds were 12.8, 4.1 and 11.0 microg ml(-1), respectively with linear response. No chromatographic interference from the tablet excipients was found. The method described in this paper was validated following the analytical performance parameters required by the USP XXIV, and was successfully applied to the commercial tablets.

Phenylpropanolamine withdrawal for decongestive uses challenged

Phenylpropanolamine withdrawal for decongestive uses challenged

Phenylpropanolamine withdrawal for decongestive uses challenged

Phenylpropanolamine withdrawal for decongestive uses challenged

Risk for Hemorrhagic Stroke with Phenylpropanolamine

Case reports since the 1970s have associated the ingestion of phenylpropanolamine (PPA), a synthetic sympathomimetic drug commonly used in appetite

Phenylpropanolamine advisory issued in the Philippines

Phenylpropanolamine advisory issued in the Philippines

Effect of Processing Methods and Heat Treatment on the Formation of Wax Matrix Tablets for Sustained Drug Release

The objective of this study was to evaluate the effects of processing methods and heat treatment on matrix formation and subsequent drug release from wax matrix tablets for controlled release. Phenylpropanolamine hydrochloride (PPA) and Compritol® were processed with appropriate diluent(s) using either dry blending (DB), wet granulation (WG), partial melt granulation (PMG), or melt granulation (MG). Then the tablets were heat-treated at 80°C. Particle size distribution and compressibility, along with drug release, tablet micro-morphology, wettability, porosity, and tortuosity were investigated. The drug release was different for the four processing methods even though the tablet formulation was identical. Heat treatment further retarded drug release and its effect was related to the previous manufacturing processes. Scanning Electron Microscopy (SEM) showed that heat treatment redistributed the wax and formed a film-like structure covering drug and excipients. The contact angle of tablets made from DB, WG, and PMG methods increased after heat treatment, while that of tablets made from DB, WG, and PMG methods increased after heat treatment, while that of tablets made from MG remained constant. Tablet tortuosity calculated from drug release rate constants increased dramatically after heat treatment. Drug release from the wax tablets with or without heat treatment was best described by the Higuchi equation. Different processing methods produced different matrix structures that resulted in different drug release rates. Heat treatment retarded drug release mainly by increasing tortuosity of the matrix. Contact angle measurement and SEM analysis indicated that heat treatment caused the wax to melt, redistribute, coat the drug and diluents, and form a network structure.

Risks with Phenylpropanolamine and Ephedra Alkaloids

Two studies highlight the risks associated with widely used sympathomimetic drugs.The first, a case-control study, was designed to assess the

Phenylpropanolamine products voluntarily withdrawn

Phenylpropanolamine products voluntarily withdrawn

Phenylpropanolamine products voluntarily withdrawn

Phenylpropanolamine products voluntarily withdrawn

Simultaneous estimation of phenylpropanolamine HCl, guaiphenesin and diphenylpyraline HCl in syrups by LC

A simple, precise and accurate HPLC method was developed for the simultaneous estimation of phenyl-propanolamine HCl, guaiphenesin and diphenylpyraline HCl in syrup. The method was carried out on a Shimpak C8 column with a mobile phase consisting of acetonitrile-triethylamine (pH adjusted to 3.5 using orthophosphoric acid; 0.5%), (35:65, v/v) at a flow rate of 1.2 ml min(-1). Detection was carried out at 210 nm. Diphenhydramine was used as internal standard. The validation of the method was also carried out.

Preparation of enteric coated timed-release press-coated tablets and evaluation of their function by in vitro and in vivo tests for colon targeting

As a new oral drug delivery system for colon targeting, enteric coated timed-release press-coated tablets (ETP tablets) were developed by coating enteric polymer on timed-release press-coated tablets composed of an outer shell of hydroxypropylcellulose and core tablet containing diltiazem hydrochloride (DIL) as a model drug. The results of the in vitro dissolution tests in JP 1st fluid (pH 1.2) and JP 2nd fluid (pH 6.8) indicated that these tablets showed both acid resistance and timed-release. To clarify whether ETP tablets could have been of use in the gastrointestinal tract, ETP tablets with a layer of phenylpropanolamine hydrochloride (PPA) (a marker of gastric emptying) between the enteric coating layer and outer shell were prepared, and were administered to beagle dogs. The gastric emptying time and lag time after gastric emptying were evaluated by determining the times at which PPA and DIL first appeared in the plasma (TFA(PPA) and TFA(DIL), respectively). TFA(PPA) and TFA(DIL) were about 4 and 7 h, respectively. This value of TFA(PPA) indicated that ETP tablets displayed acid resistance in the stomach as well as in JP Ist fluid. Subtraction of TFA(PPA) from TFA(DIL) gave a value of about 3 h which agreed well with the lag time determined by in vitro dissolution test in JP 2nd fluid. Also, the results seemed to be in accordance with the time at which the tablets reached the colon after gastric emptying. Therefore, ETP tablets seemed to be an effective tool for oral site-specific delivery including targeting of the colon.

Effect of Diluents on Tablet Integrity and Controlled Drug Release

The objective of this study was to evaluate the effect of diluents and wax level on tablet integrity during heat treatment and dissolution for sustained-release formulations and the resultant effect on drug release. Dibasic calcium phosphate dihydrate (DCPD), microcrystalline cellulose (MCC), and lactose were evaluated for their effect on tablet integrity during drug dissolution and heat treatment in wax matrix formulations. A newly developed direct compression diluent, dibasic calcium phosphate anhydrous (DCPA), was also evaluated. Compritol® 888 ATO was used as the wax matrix material, with phenylpropanolamine hydrochloride (PPA) as a model drug. Tablets were made by direct compression and then subjected to heat treatment at 80°C for 30 min. The results showed that MCC, lactose, and DCPA could maintain tablets intact during heat treatment above the melting point of wax (70°C–75°C). However, DCPD tablets showed wax egress during the treatment. MCC tablets swelled and cracked during drug dissolution and resulted in quick release. DCPD and lactose tablets remained intact during dissolution and gave slower release than MCC tablets. DCPA tablets without heat treatment disintegrated very quickly and showed immediate release. In contrast, heat-treated DCPA tablets remained intact through the 24-hr dissolution test and only released about 80% PPA at 6 hr. In the investigation of wax level, DCPD was used as the diluent. The drug release rate decreased as the wax content increased from 15% to 81.25%. The dissolution data were best described by the Higuchi square-root-of-time model. Diluents showed various effects during heat treatment and drug dissolution. The integrity of the tablets was related to the drug release rate. Heat treatment retarded drug release if there was no wax egress.

Sustained-release phenylpropanolamine hydrochloride bilayer caplets containing the hydroxypropylmethylcellulose 2208 matrix. I. Formulation and dissolution characteristics.

The purpose of this study was to develop a new sustained-release phenylpropanolamine hydrochloride (PPA) bilayer caplets that consists of an immediate-release portion and a prolonged-release portion containing a hydroxypropylmethylcellulose 2208 (HPMC2208) matrix. Since PPA is a highly water-soluble drug, incorporation of 60% HPMC2208 level in the matrix was required for giving the product a PPA-slow releasing property. Difference in the viscosity grade of HPMC2208 in the matrices did not greatly influence the PPA dissolution characteristics from the matrices. Therefore, we formulated the prolonged-release portion consisting of 10% PPA, 30% excipients, and 60% HPMC2208 (Metolose 90SH4000) into the sustained-release PPA bilayer caplets. The PPA dissolution characteristics from the formulated bilayer caplets showed the prolonged dissolution profile after rapid dissolution and was close to the targeted profile calculated from PPA pharmacokinetics study. The manufacturing methods of the prolonged-release portion and the filling order of the prolonged-release portion in bilayer compression did not significantly affect the PPA dissolution characteristics from the bilayer caplets. The PPA dissolution characteristics from the bilayer caplets was pH independent. Moreover, the PPA dissolution characteristics from the bilayer caplets was not affected by mechanical shear. The sustained-release PPA bilayer caplets is expected to present constant prolonged-release of PPA after rapid dissolution in vivo without dissolution change due to pH and mechanical shear.

Sustained-release phenylpropanolamine hydrochloride bilayer caplets containing the hydroxypropylmethylcellulose 2208 matrix. II. Effects of filling order in bilayer compression and manufacturing method of the prolonged-release layer on compactibility of bilayer caplets.

The purpose of this study was to establish the manufacturing method of the formulated bilayer caplets containing the hydroxypropylmethylcellulose 2208 (HPMC2208) matrix without lamination. In manufacturing the bilayer caplets containing the HPMC2208 (Metolose 90SH4000) matrix, some bilayer caplets were cracked. We found that cracking of bilayer caplets is not the separation of two layers, but lamination of the prolonged-release layer. It was assumed that Metolose 90SH4000 causes lamination of the prolonged-release layer. Two factors, roller compaction pressure on dry granulation of the prolonged-release layer and filling order of the prolonged-release layer in bilayer compression, were related to lamination of bilayer caplets. The compactibility of the prolonged-release layer decrease with an increase in roller compaction pressure on dry granulation. The compactibility of the prolonged-release layer manufactured by direct compression is superior to that manufactured by dry granulation. The compactibility of the prolonged-release layer in the shape of the second layer, convexo-concave, is superior to that in the shape of the first layer, convexo-convex. This is due to the fact that the density distribution inside the compact in the shape of convexo-concave was more uniform than that in the shape of convexo-convex. The manufacturing method of the formulated bilayer caplets having the prolonged-release layer whose Metolose 90SH4000 content is 60% without lamination is as follows: the prolonged-release layer manufactured by direct compression is fed as the second layer in bilayer compression.