Influence of excipients, drugs, and osmotic agent in the inner core on the time-controlled disintegration of compression-coated ethylcellulose tablets.
The effect of excipient, drug, and osmotic agent loaded in the inner core tablet on the time-controlled disintegration of compression-coated tablet prepared by direct compression with micronized ethylcellulose was investigated. The excipients [spray-dried lactose, hydroxypropyl methyl cellulose, sodium starch glycolate, microcrystalline cellulose, different drugs (sodium diclofenac: model drug, salbutamol sulfate, and theophylline anhydrate) and osmotic agent (sodium chloride)] were used to formulate the composition of the inner core tablet. The result indicates that drug release from all the compression-coated tablets was characterized by a distinctive lag of time followed by a faster drug release, dependent on the types of excipient and drug, and osmotic agent used in the inner core tablet. Respectively, the lag of time was 8.5, 12.4, 14.6, or 15.8 h for spray-dried lactose, hydroxypropyl methyl cellulose, sodium starch glycolate, or microcrystalline cellulose-loaded inner core tablet, as compared with 16.4 h for an inner core made of sodium diclofenac alone. The direct-compressible excipients such as spray-dried lactose, sodium starch glycolate, and microcrystalline cellulose seemed not to illustrate a marked disintegration function to rapidly rapture the outer coating layer. The lag of time was only slightly shortened from 16.4 to 14.6 h, >24 to 17.8 h, or >24 to 21.3 h for sodium diclofenac, theophylline anhydrate, or salbutamol sulfate incorporated with sodium starch glycolate into the inner core tablet, respectively, suggesting that sodium starch glycolate did not perform its superdisintegration. Once an osmotic agent of sodium chloride was incorporated into the inner core tablet, the lag of time for the compression-coated tablet was markedly shortened to <1 h, as compared with 16.4 h for drug alone. The more the amount of sodium chloride added, the less the time of lag obtained. Osmotic pressure did have a key role in controlling the drug dissolution. The present result implies that osmotic function is more suitable than superdisintegration function in designing a compression-coated tablet with time-controlled disintegration.
Lin
Shan-Yang
SY
Biopharmaceutical Laboratory, Department of Medical Research & Education, Veterans General Hospital-Taipei, Taipei, Taiwan, Republic of China. sylin@vghtpe.gov.tw
Lin
Kung-Hsu
KH
Li
Mei-Jane
MJ
D000420:Albuterol / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004008:Diclofenac / Q000737:chemistry; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D006244:Hardness; D007700:Kinetics; D009995:Osmosis; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011208:Powders; D011312:Pressure; D012965:Sodium Chloride / Q000737:chemistry*; D012995:Solubility; D013607:Tablets; D013806:Theophylline / Q000737:chemistry; D013997:Time Factors
D003692:Delayed-Action Preparations; D005079:Excipients; D004364:Pharmaceutical Preparations; D011208:Powders; D013607:Tablets; D004008:Diclofenac; D012965:Sodium Chloride; C013517:ethyl cellulose; D002482:Cellulose; D013806:Theophylline; D000420:Albuterol