Propranolol hydrochloride

Chemical Name 1-(isopropylamino)-3-(1-naphthyloxy)-2-propanol hydrochloride Common Name — 

Trade Name Manufacturer Country Year Introduced 

In a first step, 1-naphthol was reacted with epichlorohydrin to give 1-chloro-3-(1-naphthoxy)-2-propanol. 

A mixture of 4.4 parts of 1-chloro-3-(l-naphthoxy)-2-propano and 16 parts of isopropylamine is heated in a seaied vessel at 70° 80°C for 10 hours. The vessel is cooled and to the contents there are added 50 parts of water. The mixture is acidified with 2 N hydrochloric acid, and washed with 50 parts of ether. The aqueous phase is decolorized with carbon, and then added to 50 parts of 2IM sodium hydroxide solution at 0°C. The mixture is filtered. The solid residue is washed with water, dried, and crystallized from cyclohexane. There is thus obtained l-isopropylamino-3-(1-naphthoxy)-2-propanol, MP 96°C. 

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Propranolol. Propranolol hydrochloride, considered the prototype of the P-adrenoceptor blocking agents, has been in use since 1964. It is a nonselective, highly Hpid-soluble P-adrenoceptor blocker having no ISA. It is a mixture of (+) and (—) enantiomers, and the (—) enantiomer is the active moiety. The local anesthetic effects of propranolol are equipotent to those of Hdocaine [137-58-6] C 4H22N20, (see Anesthetics). Therapeutic effects include termination of catecholamine-induced arrhythmias, conversion of SA nodal tachycardias (including flutter and fibrillation) and AV nodal tachyarrhythmias to normal sinus rhythm, digitahs-induced arrhythmias, and ventricular arrhythmias (1,2). The dmg also has cardioprotective properties (37,39). 

FIG. 17 Chemical structures of (a) epinephrine hydrochloride, (b) dopamine hydrochloride, (c) isoproterenol hydrochloride, (d) phenylephrine hydrochloride, (e) tolazoline hydrochloride, (f) oxyprenolol hydrochloride, (g) alprenolol hydrochloride, and (h) propranolol hydrochloride. 

ND Eddington, M Ashraf, LL Augsburger, JL Leslie, MJ Fossler, LJ Lesko, VP Shah, GS Rekhi. Identification of formulation and manufacturing variables that influence in vitro dissolution and in vivo bioavailability of propranolol hydrochloride tablets. Pharm Dev Tech 3(4) 535-547, 1998. 

Ubrich, N., Bouillot, Ph., Pellerin, Ch., Hoffman, M. and Maincent Ph. (2004) Preparation of propranolol hydrochloride nanopartides a comparative study. Journal of Controlled Release, 97 291-300. 

Class n, beta-adrenergic blocking agents esmolol hydrochloride propranolol hydrochloride sotalol hydrochloride... 

Beta-adrenergic blocking agents propranolol hydrochloride... 

This paper reports the effect of pH, electrolytes and drugs on the cloud points of HPMC gels and the effect of these electrolytes on the dissolution of propranolol hydrochloride from HPMC matrices and on the disintegration of HPMC matrices containing no drug. 

Propranolol hydrochloride and promethazine hydrochloride increased the gel points and no straight line relationship existed, indicating that at higher concentrations these drugs enable the polymer to hydrate to a much larger extent than at lower concentrations. Promethazine forms micelles at concentrations. 5% w/v [9], which may be responsible for this behaviour. No critical micellar concentration is known for propanolol hydrochloride but from studies performed it is weakly surface active. The response of HPMC to these drugs may be associated with this surface activity. 

Table 5—The effect of solute and ionic strength in the dissolution rate of propranolol hydrochloride from K15M matrix tablets...

Topical release and permeation studies of propranolol hydrochloride from hydrophilic polymeric matrices... 

In the light of these observations and the newer trends in product formulation, it was decided to study the in vitro release and permeation of propranolol hydrochloride from various hydrophilic polymeric matrices using the cellulose membrane and the hairless mouse skin as the diffusion barriers and to evaluate the effects of some of the additive ingredients known to enhance drug release from dermatological bases. 

All ingredients of the individual formulation as shown in Table 1 were accurately weighed for the batch size. The polymer was slowly dispersed in a portion of previously heated water at 80 2°C and another portion of water at room temperature was added and mixed. Propranolol hydrochloride and other ingredients including additives were predissolved and then incorporated in the batch at 40 2°C. All samples prepared were then stored in glass containers. 

Plots of absorbance vs. wavelength for solutions of propranolol hydrochloride in water and buffer pH 6, USP [21], were developed. The maximum absorbance values observed were 290 nm for water and buffer solutions of the drug. Beer s law was followed for l-20pg/ml concentrations. The... 

All samples prepared were analysed for propranolol hydrochloride content. Only samples with 100% 10% drug contents were used in these studies. 

In vitro release data of propranolol hydrochloride from the four formulations evaluated ovr a 24 h period are shown in Table 2. The decreasing rank order of drug release from these samples was observed to be as follows Methocel matrix> Avicel CL-611 matrix>PVA-gelatin matrix>emulsion base. The Methocel matrix, formulation A, exhibited the maximum release of the drug, whereas the drug released was at a minimum from the PVA-gelatin matrix, formulation... 

C. This could be attributed to the possible cross-linkages formed between the two polymers which thus restricted the movement of the drug molecules within the gel. The release of propranolol hydrochloride from the emulsion base, formulation D, was relatively low compared with all the hydrophilic polymeric gel formulations. This suggests that, for a water-soluble drug such as propranolol hydrochloride, polymeric-gel-based formulations are clearly the better vehicles for developing such dosage forms. 

Fig. 1—Diffusion profile of propranolol hydrochloride as a function of square root of time (tl/2) from different polymeric matrices , Methocel matrix 0, Avicel CL-611 matrix , PVA-gelatin matrix o, emulsion base.

Table 3—In vitro release-permeation of propranolol hydrochloride from Methocel matrix formulation in the presence of the additive ingredients using cellulose membrane...

Table 5 Drug release from Methocel matrix formulation containing varied concentrations of propranolol hydrochloride...

Fig. 2—Effect of drug loading on the release profile of propranolol hydrochloride from Methocel matrix (V), 3.0% 0,2.0% , 1.0% o,0.5%.

Table 6—Effect of DMSO on the permeability of propranolol hydrochloride from Methocel matrix diffusion experiment through hairless mouse skin...

Fig. 3—Diffusion profile of propranolol hydrochloride as a function of time (t) from Methocel matrix through hairless mouse skin , matrix+skin o, matrix (5% DMSO)+skin , matrix+skin soaked in DMSO for 1 h.

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