Various sustained-release drug-delivery and drug-targeting systems are becoming increasingly important for minimizing drug
degradation and loss, preventing harmful side effects, increasing drug bioavailability and delivering drug to the required
site in the body. Among the various novel drug-delivery systems available, oral controlled-release systems are widely accepted
because of their ease of administration, reduced dose and dosing frequency, stable drug levels, effectiveness in the treatment
of chronic disease, and convenience for patients due to the systems' simplified dosing schedule (1).
Dosage forms that can be retained in the stomach are called gastroretentive drug-delivery systems (GRDDS). GRDDS are effective
for localized drug delivery, lowering the incidence of gastric side effects, reducing irritation (because a small amount of
drug is exposed to gastric mucosa at a specific time), and improving the controlled delivery of drugs that have an absorption
window, thereby ensuring optimal bioavailability (2, 3).
This article focuses on a study involving a GRDD formulation using ibuprofen as a model drug. Ibuprofen is a prominent nonsteroidal
anti-inflammatory drug used extensively to treat various musculoskeletal and joint disorders, mild to moderate pain, periarticular
disorders, soft-tissue disorders, and fever. It also is used as an alternative to indomethacin to treat patent ductus arteriosus
(4). The usual treatment amount for painful conditions is between 600 mg and 1.8 g daily in several doses. Patients with rheumatoid
arthritis generally require higher doses of ibuprofen than those with osteoarthritis (5). The recommended dose for fever reduction
in adults is 200–400 mg every four to six hours to a maximum of 1.2 g daily (4).
The drug has proven therapeutic efficacy, tolerability, and safety, and is, therefore, the drug of first choice in the management
of these conditions (6). The drug's short plasma half-life (i.e., 2 h) necessitates frequent oral dosing to maintain the desired
steady-state level, and this frequency can cause poor patient compliance (7). Furthermore, conventional dosage forms do not
provide protection against early-morning joint stiffness, which is common in rheumatoid states (8). Thus, administering such
a drug as a modified-release dosage form provides clinical benefit and related advantages. Because of the low amount of drug
in the stomach, the controlled release of ibuprofen reduces risk of local irritation, compared with conventional dosage forms
Ibuprofen was obtained as a sample from Alkem Laboratories (Mumbai). Hydroxypropyl methylcellulose (HPMC) K4M and K15M grades,
carbomer 934P grade, and sodium bicarbonate were purchased from Central Drug House (Delhi, India). Polyvinyl pyrrolidone K30
grade, lactose, magnesium stearate, and purified talc were purchased from Loba Chemie (Mumbai). The purity and chemical structure
of the chemicals are summarized in Table I. All other chemicals and reagents used in the study were of analytical grade. The
authors conducted Fourier transform infrared spectroscopy studies to assess the ingredients' compatibility. Ibuprofen was
incompatible with polyvinyl pyrrolidone, so Carbopol was used as binder. Magnesium stearate also was incompatible with ibuprofen
at concentrations greater than 5%.
Table I: List of chemicals and their purities. (ALL IMAGES ARE COURTESY OF THE AUTHORS)