Formulation and Evaluation of Press Coated Tablets for Pulsatile Drug Delivery Using Hydrophilic and Hydrophobic Polymers

Abstract

Pulsatile drug delivery systems (PDDS) are gaining importance as these systems deliver the drug at specific time as per the pathophysiological need of the disease, resulting in improved patient therapeutic efficacy and compliance. These systems are beneficial for the drugs having chronopharmacological behaviour (where night time dosing is required), firstpass effect and having specific site of absorption in gastro intestinal tract (GIT). From the viewpoint of therapeutic optimization, maintaining a constant blood level for a drug in the human body is questionable.1) Long-term constant drug concentration exposed in blood and tissues may induce many problems such as tolerance of drug and activation of physiological system.2) Recently, chronotherapy has been extensively applied in clinical therapy by modulating the dosing regimen of drug administration according to physiological needs.3) Diseases wherein PDDS are promising include asthma, peptic ulcer, cardiovascular diseases, arthritis, and hypercholesterolemia. The pathophysiology of arthritis and patients with osteoarthritis tend to have less pain in the morning and more at night; while those with rheumatoid arthritis, have pain that usually peaks in the morning and decreases throughout the day. 4)A dry-coated tablet was recently renewed as a novel system to deliver a drug in a pulsatile way, at predetermined times following oral administration. 4,5) This novel system is not only rate controlled but is also time controlled. The dry-coated tablets were prepared by a direct compression method. This compression method eliminates the time-consuming and complicated coating or granulation processes and also improves the stability of the drug by protecting it from moisture. 6)There are various problems with pH dependent drug delivery; however the pH in the gastrointestinal tract varies between and within individuals. [7][8][9] It is affected by diet and disease.10) During acute stage of inflammatory bowel disease colonic pH has been found to be significantly lower than normal.11) In ulcerative colitis pH values 2.3-4.7 have been measured in the proximal parts of the colon.12)The purpose of this study was to develop press coated tablets for pulsatile drug delivery of ketoprofen. The oral press coated tablet was developed to achieve the time-controlled disintegrating or rupturing function with a distinct predetermined lag time. Press-coated tablet containing ketoprofen and other excipients in the inner core was formulated with an outer shell by different weight ratios of hydrophobic polymer (micronized ethylcellulose powder) and hydrophilic polymers (glycinemax husk, sodium alginate). Ethylcellulose (EC) is a well-known water-insoluble polymer that has been used as a rate-controlling membrane to regulate drug release. EC powder with different micronized sizes has been directly compressed to form compact EC in which plastic deformation is the predominant consolidation mechanism.13) Glycinemax containing dry matter (DM), crude protein (CP), crude fiber (CF), ether extract ...

Oral pulsatile delivery: Rationale and chronopharmaceutical formulations

“…Indeed, larger particle dimensions were associated with a higher porosity thus resulting in enhanced shell permeability. As expected, the incorporation of swellable (HPMC, sodium starch glycolate, sodium alginate, glycine max husk) and osmotic (sodium chloride) excipients into the core formulation or of hydrophilic compounds (HPMC, spray-dried lactose) into the outer shell was reflected in shorter delay phases (Lin et al, , 2004aRane et al, 2009). Modifications of half of the coating formula were demonstrated to be a further means of modulating the lag phase.…”

“…Interestingly, when EC was replaced by Eudragit ® RL, floating dosage forms were obtained because of the higher water permeability and flexibility characteristics of the films. EC was also applied by double-compression technique (Lin et al, 2001a,b;Rane et al, 2009). In these cases, the delayed onset of release was related to the split of the coating shell into two halves following formation of symmetrical breaches within its lateral structure due to a hypothetically lower inherent packing density.…”

Effect of HPMC and ethyl cellulose polymeric granules and its combinations in press coated tablets of lornoxicam: fabrication and in vitro characterization

“…The disc was placed in the sample holder and scanned from 4000 to 500 cm -1 at a resolution of 1 cm -1 (Rane et al, 2009) …”

Investigating effects of hydroxypropyl methylcellulose (HPMC) molecular weight grades on lag time of press-coated ethylcellulose tablets

“…A swellable core encapsulated by rupturable outer coat, engineered using a combination of water soluble and water insoluble polymers, can be contrived to fabricate a time-controlled PR formulation [12][13][14][15] . Various coating strategies such as pan coating, fluidized bed coating, compression coating, and so on can be employed to achieve a desired lag time which is the key element of a PR formulation [2][3][4]6,10 .…”