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Semi-solid dosage form of clonazepam for rapid oral mucosal absorption

Published on Jul 1, 2011in Drug Development and Industrial Pharmacy2.367
· DOI :10.3109/03639045.2010.545069
Osamu Sakata6
Estimated H-index: 6
(Hoshi University),
Yoshiharu Machida38
Estimated H-index: 38
(Hoshi University),
Hiraku Onishi14
Estimated H-index: 14
(Hoshi University)
Abstract
Background: In order to obtain an alternative to the intravenous (i.v.) dosage form of clonazepam (CZ), an oral droplet formulation of CZ was developed previously; however, the droplet was physically unstable. Therefore, in the present study, it was attempted to develop an easily-handled dosage form, which was more physically stable and allowed rapid drug absorption from oral mucosa. Method: A semi-solid dosage form, composed of polyethylene glycol 1500 (PEG), CZ, and oleic acid (OA) at 37/1/2 (w/w) and named PEG/CZ/OA, and a semi-solid dosage form containing PEG and CZ at 39/1 (w/w), called PEG/CZ, were prepared. Their physical stability in air at room temperature and oral mucosal absorption in rats were investigated. Results: The semi-solid dosage forms were much more stable physically than the droplet, that is, no recrystallization of CZ was observed for at least 8 days. The effective concentration for humans and rats (20 ng/mL or more) was achieved within 30 min after buccal administration for both PE...
  • References (17)
  • Citations (4)
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References17
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#1Jennifer R. Riss (UMN: University of Minnesota)H-Index: 5
#2James C. Cloyd (UMN: University of Minnesota)H-Index: 29
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Benzodiazepines (BZDs) remain important agents in the management of epilepsy. They are drugs of first choice for status epilepticus and seizures associated with post-anoxic insult and are also frequently used in the treatment of febrile, acute repetitive and alcohol withdrawal seizures. Clinical advantages of these drugs include rapid onset of action, high efficacy rates and minimal toxicity. Benzodiazepines are used in a variety of clinical situations because they have a broad spectrum of clini...
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#1Osamu Sakata (Hoshi University)H-Index: 6
#2Hiraku Onishi (Hoshi University)H-Index: 24
Last. Yoshiharu Machida (Hoshi University)H-Index: 38
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Oral droplet formulations of clonazepam (CZ) were developed to examine their potentials as an alternative to i.v. administration for the treatment of acute epileptic seizures. Propylene glycol containing 2.5% (wt/wt) CZ with or without 5.0% (wt/wt) oleic acid (OA) was prepared as a solution by heating at 90°C and subsequently lowering the temperature to 30°C. The droplet (20 μL) was administered to the oral cavity between the lower gum and bottom lip before CZ precipitation started. With a dropl...
7 CitationsSource
Recent remarkable progress in genomic novel drug discovery enables us to prepare drug candidates with tremendous diversity in a high-throughput-manner. In clinical use of these candidates, they should be effectively delivered to a target-tissue in body. But delivery systems suitable for the high-throughput discovery of drugs have never been established. Tight junctions (TJs) play a pivotal role in compartmentation of each tissues and maintenance of their intra-circumstances. Claudin, a membrane ...
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#1R.a.j. Birudaraj (UOP: University of the Pacific (United States))H-Index: 1
#2Bret Berner (Depomed)H-Index: 10
Last. Xiaoling Li (UOP: University of the Pacific (United States))H-Index: 18
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Abstract The transport of buspirone across porcine buccal mucosa in vitro was investigated to elucidate the mechanisms of transport and permeation enhancement. The apparent permeability increased with an increase in pH to a lesser degree than the dependence of the partition coefficient. Whereas the lipophilic or apparent transcellular pathway was found to be the dominant buccal transport route for buspirone, ionized species contributed significantly to transport at acidic pH. At neutral pH, bile...
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#1Hiraku Onishi (Hoshi University)H-Index: 24
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The oral patch of diazepam (DZ) was developed to achieve a rapid absorption of DZ for the emergency treatment of epileptic seizure or anxiety disorder. The patch was composed of the outer mucoadhesive Carbopol 934 region, central drug region, and Tegaderm backing film. DZ (3 mg) was dissolved in propylene glycol (PG) alone or PG containing oleic acid (OA) at 5.6% (w/w), and used as the drug region. The patches with and without OA were attached to the mucosa of cheek in rats. The patch with OA ex...
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Abstract The acute effects of low-dose clonazepam on seizure frequency in children with epilepsy was evaluated. In an open study, 19 children with epilepsy (15 generalized and four partial) were examined during hospitalization with recordings of seizures by trained personnel. Seizures were counted during two 24-hour periods: before and after a single intramuscular injection of clonazepam 0.01-0.04 mg/kg body weight. Plasma concentrations of clonazepam were determined. The median number of seizur...
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#1Lianli Li (St. John's University)H-Index: 3
#2Sudhir R Gorukanti (St. John's University)H-Index: 2
Last. Kwon H. Kim (St. John's University)H-Index: 10
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Intranasal (IN) administration is a promising approach for rapid-onset delivery of medications. In order to assess the feasibility of this approach for the emergency treatment of status epilepticus, three anticovulsants, i.e. diazepam (DZ), clonazepam (CZ), and a monocarbamate-based new compound (MCA) were studied in rabbits for the pharmacokinetics (PK) and pharmacodynamic (PD) response following intravenous (IV) and IN administrations. The animals were intranasally dosed with DZ (1 mg/kg), CZ ...
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#2Jean-Marc TréluyerH-Index: 35
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All benzodiazepines enter cerebral tissue rapidly. However, the duration of action is short for diazepam (<2 hours) and midazolam (3 to 4 hours) and longer for clonazepam (24 hours) and lorazepam (up to 72 hours), and is not correlated with the plasma concentration-time profiles of these drugs. Although a relationship between the plasma concentration of diazepam, lorazepam and midazolam and their pharmacodynamic effect has been demonstrated in healthy individuals, some caution is warranted as th...
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#1Michelle Franz-Montan (State University of Campinas)H-Index: 14
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