SUSTAINED RELEASE QUINIDINE DOSAGE FORM

Abstract: A sustained release quinidine dosage form comprising a plurality of pellets of an average diameter not greater than about 1 mm. Each pellet comprises a coating of quinidine over a nonpareil seed which is then coated with a mixture of about 3 to about 9 parts by weight ethylcellulose to about 1 part by weight hydroxypropylcellulose. The sum of such pellets in a container constitutes a single sustained release dosage unit of quinidine.

Description: Sustained Release Quinidine Dosage Form Summary of the Invention Quinidine is a well known alkaloid used in the treatment of certain cardiac arrhythmias. It is a general cardiac depressant, which reduces myocardial excitability, automaticity and conductivity. In accordance with the present invention there is provided a sustained release quinidine dosage form which which comprises a container having therein a plurality of pellets having an average diameter not greater than about 1 mm. Each pellet has a coating of quinidine over a nonpareil seed. The quinidine-coated nonpareils are then coated with a mixture of about three to about nine parts by weight ethylcellulose to about one part by weight hydroxypropylcellulose. The present invention provides a sustained release quinidine dosage form, typically, a capsule containing from about 2,000 to about 15,000 of the polymer-coated pellets. Each of the pellets is based upon a nonpareil, which is typically a sugar seed having a mesh of about 20 to about 25. The nonpareils are coated with more than an equal amount by weight of a quinidine compound, which prefer¬ ably is quinidine bisulfate. In a preferred embodiment, about two parts by weight quinidine bisulfate are coated onto one part by weight of nonpariel seeds. In one embodiment, 500 g nonpareil seeds are placed in a coating pan and wetted with a 30% sucrose solution with the aid of a sprayer. Approximately 30 g of quinidine bisulfate are dusted onto the thus-treated pellets, distributing the material manually as necessary. Wet¬ ting and dusting procedures are repeated until a buildup OMP S WWHHF of 1000 mg of quinidine bisulfate takes place per 500 gm of the nonpareils. When coated with a greater than equal weight of quinidine, the thus quinidine-coated nonpareil seeds are coated with a sustained release polymeric coating mix, which comprises from about three to about nine parts by weight of ethyl cellulose to about one part by weight hydroxypropylcellulose. In one embodiment, 700 gm of quinidine bisulfate- nonpareils (2:1 weight ratio) , produced above, are charged into an air suspension coating column (Wurster column, six inches, manufactured by Glatt Air Techni¬ ques) and after commencement of the air suspension of these pellets, there is charged into the air suspension a spray of methanol-chloroform (380 ml methanol; 1400 ml chloroform) which contains 66.8 mg mixture of ethylcel¬ lulose (Ethocel type 10, Dow Chemical Co.) and hydroxy¬ propylcellulose (Klucel LF, Hercules) , this mixture having a weight ratio of 7 parts ethylcellulose to 3 parts hydroxypropylcellulose. Typical conditions useful for preparing the poly¬ meric coating of the pellets in the above-described equipment include a 40°C inlet temperature, 2 bar spray air pressure and a liquid feed rate of 12cc per minute. Pellets produced in accordance with the procedures set forth above yield a sustained release over a pro¬ longed period of time. When tested according to U.S.P. XX dissolution procedure (one hour in simulated gastric fluid followed by simulated intestinal fluid) the fol¬ lowing release characteristics are noted: OMPI Time (hrs.) Percent Release 1 6.0 2 20.1 4 43.1 6 64.5 8 84.1 10 96.1 12 99.9 The formulation of the present invention is partic¬ ularly advantageous for pediatric and geriatric patients who may be either unable or unwilling to swallow a larger sustained release tablet. For pediatric adminis¬ tration it is particularly contemplated that the indi¬ vidually coated polymeric pellets are administered in food.

Claims: WHAT IS CLAIMED: 1. A sustained release quinidine dosage form which comprises a container having therein a plurality of pellets, the average pellet diameter not greater than about 1 mm, each pellet comprising a coating of quini¬ dine over a nonpareil seed, the thus quinidine-coated nonpareils are coated thereon with a mixture of about 3 to about 9 parts by weight ethylcellulose to about 1 part by weight hydroxypropylcellulose, the sum of such pellets in a container form a single dosage unit of quinidine. 2. A sustained release quinidine dosage form of claim 1 wherein said quinidine is in the form of quini¬ dine bisulfate. 3. A sustained release quinidine dosage form of claim 1 wherein the weight of quinidine is approximately twice that of the nonpareil. 4. A sustained release quinidine dosage form of claim 1 wherein said container is a capsule.

Inventors: HSIAO CHARLES, HSIAO, CHARLES
Applicants: KEY PHARMA, KEY PHARMACEUTICALS, INC.
Application year: 1983
Main classification: A61K9
IPC codes: A61K9, A61K31