The Effect of Core and Coating Composition on Drug Release from Directly Compressed Time-Controlled Release Tablets

The authors prepared and tested press-coated tablets with various weight ratios of ethylcellulose to hydroxypropylcellulose (HPC) and various ratios of two different batches of HPC as an outer coating shell and fillers in core tablets. The tablets were examined for changes in time lag and release patterns of salbutamol sulfate.
Apr 02, 2007
Volume 31, Issue 4

Time-controlled and pulsatile releases are increasingly being considered as desirable modes of drug delivery because there is a growing awareness of the importance of circadian rhythms with respect to physiology, disease state, and drug action that has given rise to the related fields of chronopharmaceutics and chronopharmacology (1, 2). At present, the drug must be administered not only in the right amount at a proper rate but also at the right time. For many drugs, including antiasthmatic, antihistaminic, psychotropic, anaesthetic, cardiovascular active drugs, and nonsteroidal anti-inflammatory drugs, significant daily variations in pharmacokinetics or drug effects have been demonstrated in man, depending on physiological or physiopathological changes of circadian rhythmicity (3). Nocturnal symptoms and overnight decrements in lung function are a common part of the asthma clinical syndrome. Circadian changes are seen in normal lung function, which reaches a low point in the early morning hours. This dip is particularly pronounced in people with asthma. Because bronchoconstriction and exacerbation of symptoms vary in a circadian fashion, asthma is well suited for chronotherapy. Chronotherapies have been studied for asthma with oral corticosteroids, theophylline, and β2 -agonists. Treatment strategies for nocturnal asthma are similar to those used to treat persistent asthma, although it is beneficial to dose medications to target optimum effect during periods of nocturnal worsening (4). The study has been carried out with salbutamol sulfate as an antiasthmatic drug.

Table I: Composition of core tablets.
Several studies have been published in which tablet cores were coated with directly compressed micronized ethylcellulose (EC) (5–7) and hydroxypropylcellulose (HPC) (8). There have been no published studies, however, involving the use of various grades of HPC (erodible and gellable polymer) combined with commercial grades of EC (rupturable polymer) on timed-release preparations, regardless of giving different release mechanisms of drug with different core composition.

The main objective of this study was to investigate whether compression coating could be used to produce tablets providing maximum in vitro drug release within 6–8 h after an evening dose taken at approximately 22:00. The basic idea behind the dosage-form development is to investigate the effect of core and coating composition on lag time and drug release from a directly compressed time-controlled release tablet.

Materials and methods

Materials. Salbutamol sulfate was chosen as a model drug and was a gift from Cipla Ltd. (Kurkumbh, India). Hydroxypropyl-cellulose (HPC HF and HPC EXF, batches 3523 and 4942, respectively), ethylcellulose (ECN 22 F, batch 40900), spray-dried compound of α-lactose monohydrate and maize starch (Starlac, batch YM007), microcrystalline cellulose (Avicel PH 101, batch 6442C), and croscarmellose sodium (Ac-Di-Sol, batch 7691) were gifts from Signet Chemicals (Mumbai, India). Magnesium stearate and colloidal silicon dioxide (Aerosil 200) were purchased from S.D. Fine Chemicals (Mumbai, India). The colorant Sunset Yellow was obtained as a gift from Ranbaxy Ltd. (Jejuri, India). All other reagents were of analytical grades.

Preparation of core tablets. The inner-core tablets were prepared using direct compression to perform various release kinetics, depending upon the release mechanism involved. Powder mixtures of salbutamol sulfate, Starlac, or Avicel PH 101, Ac-Di-Sol, and Sunset Yellow were dry blended for 20 min followed by the addition of magnesium stearate and Aerosil. The mixtures were further blended for 10 min and then compressed into tablets (average tablet weight = 75 mg) using a rotary tablet machine equipped with 6-mm concave faced punch. Sufficient pressure was applied to keep the hardness at 5 ± 0.33 kg/cm2 . Table I lists the core compositions for one tablet.

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