Development of an Osmotically Controlled Drug-Delivery System of Glipizide

The authors describe the development of an inclusion complex of GLZ and formulated an extended-release dosage form based on osmotic technology.
Nov 02, 2010
Volume 34, Issue 11

The earliest studies in the field of modified drug delivery date back to the 1950s. Since then, a large number of drug products, mainly in the form of tablets and capsules with controlled-release characteristics, have been introduced. Das and Das predicted a minimum growth of 9% per year for this market through 2007 (1). Various technologies have been investigated to achieve the different types of modified release (e.g., sustained, delayed, pulsatile, targeted, and programmed release). Regardless of the delivery type, the primary mechanisms associated with drug transport in these systems are diffusion, swelling, erosion, ion exchange, and osmotic-transport effect. These mechanisms have been investigated in several studies (2–7).

Glipizide (GLZ), a weak acid (pKa = 5.9) is practically insoluble in acidic environments, highly permeable, and insoluble in water (39 µg/mL). Oral absorption of GLZ is uniform, rapid, and complete; its bioavailability is nearly 100%, and its elimination half-life is 2–4 h (8).

Class II compounds such as GLZ comprise relatively lipophilic and water-insoluble drugs with saturated solubility ≤0.1mg/mL that, when dissolved, are well absorbed from the gastrointestinal tract. Commonly, drugs in this class have variable bioavailability because of the influence of formulation effects and in vivo variables on absorption (9). Scientists try various formulation techniques such as nanoparticles, the addition of surfactants, salt formation, and complexation to change the drugs to Biological Classification System Class I compounds (9–11). Complexation with cyclodextrins (CDs) has been widely used to improve the solubility and dissolution rate of poorly water-soluble drugs (12). CDs also enhance drugs' physical and chemical stability and eliminate unpleasant odors and tastes (13).

Many methods are available for determining the physical nature of an inclusion complex. The inclusion complex can be characterized in the solid state by techniques such as Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) (14). A complex prepared using the solvent-evaporation method in a 2:1 ratio of hydroxypropyl (HP)–β–CD to GLZ enhanced solubility and dissolution. The result could be used to formulate an osmotic-pump tablet.

In the 1970s, Theeuwas introduced an elementary osmotic-pump tablet (EOPT) (2). Because an EOPT is simple to prepare and drug release can be controlled over an extended period, interest in developing EOPTs increased over the past two decades. However, the generic EOPT is only suitable to deliver drugs of moderate solubility. Okimoto investigated osmotic-pump tablets for poorly water-soluble drugs (e.g., testosterone, prednisolone, and chlorpromazine) using sulfobutyl ether-β-cyclodextrin (SBE) 7m-β-CD as a solubilizer and osmotic agent (12, 15).

The authors aimed to develop a new EOPT of GLZ with proper accessorial material after making an inclusion complex of it with HP–β–CD to increase its solubility and deliver it over an extended period of time.


GLZ, microcrystalline cellulose, dicalcium phosphate, spray-dried lactose monohydrate NF, magnesium stearate, and talc were donated by Sword and Shield Pharmaceutical (Chhatral, Gujarat, India). The sample of HP–β –CD (molecular weight of 15000 Da) was a gift from Roquette (Lestrem, France). Sodium chloride and potassium chloride were purchased from S.D. Fine Chem (Mumbai). Various grades of hydroxypropyl methylcellulose (HPMC) were donated by Colorcon Asia Pacific (Singapore). All chemicals and solvents were of analytical-reagent grade.

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