Formulation and Evaluation of an Effervescent, Gastroretentive Drug-Delivery System

The authors developed a formulation for effervescent gastroretentive drug delivery techniques using ibuprofen as a model drug. They optimized the formulations by applying full factorial design.
Oct 02, 2010
Volume 34, Issue 10

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 (9).


Table I: List of chemicals and their purities. (ALL IMAGES ARE COURTESY OF THE AUTHORS)
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%.

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