Preparation and Characterization of Meloxicam–Myrj-52 Granules Obtained by Melt Granulation - Pharmaceutical Technology

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Preparation and Characterization of Meloxicam–Myrj-52 Granules Obtained by Melt Granulation
Various manufacturing techniques can improve a drug's solubility, thus increasing its bioavailability. The authors examined whether melt granulation can enhance drug solubility using meloxicam as the drug substance and myrj-52 as the binder.


Pharmaceutical Technology



AUTHORS
The rate and extent of dissolution of the active ingredient in any dosage form is often considered the rate and extent of absorption of the drug (1). In cases such as poorly water soluble drugs, dissolution may be the rate-limiting step in the absorption process. Drugs with poor aqueous solubility such as piroxicam absorb slowly compared with drugs with higher solubility (2). One can develop formulations to increase a drug's water solubility.

Interest in melt granulation has increased because of the technique's advantage over traditional wet granulation. The melt-granulation process uses a substance that melts at relatively low temperatures (i.e., 50–80 C). This substance can be added to the molten form over the substrate or to a solid form, which is then heated above its melting point by hot air or by a heating jacket. In both cases, the substance acts like a liquid binder after it melts. Thus, melt granulation does not require organic or aqueous solvents (3). The main advantage of not using organic solvents is the absence of any risk originating from residual solvents. Moreover, the drying step is not necessary in melt granulation, thus the process is less time-consuming and more energy-efficient than wet granulation.

After selecting a suitable binder, one can use melt granulation to prepare controlled-release or improved-release granules. Many hydrophobic excipients have been used to prepare controlled-release granules. Polyethylene glycol is used to improve dissolution because it is hydrophilic in nature (4–7).

Polyoxyl stearates may be considered as potentially useful hydrophilic binders in melt granulation (8). Polyoxyl stearates are a series of polyethoxylated derivatives of stearic acid. They are nonionic, hydrophilic surfactants produced by the polyethoxylation of stearic acid. Polyoxyl-40 stearate is waxy and solid and has a faint odor of fat. Its color ranges from off-white to light tan. It has a particularly low melting point (38 C) and is mainly used as an emulsifying agent, solubilizing agent, and wetting agent.

Meloxicam [4-hydroxy-2 methyl-N-(5-methyl-2-thiazolyl)-2H-1, 2-benzothiazine-3-carboxamide 1, 1-dioxide] is a nonsteroidal anti-inflammatory drug used to treat rheumatoid arthritis, osteoarthritis, and other joint pains. It is a preferred COX-2 inhibitor with superior gastrointestinal tolerability (9). Meloxicam has poor dissolution in aqueous fluids, especially in acidic mediums. Many studies have been performed to improve meloxicam's dissolution and bioavailability (10–12).

The goal of this investigation was to improve the dissolution rate of meloxicam through melt granulation using water-soluble myrj-52 as a meltable binder. The authors investigated the in vitro release of the drug from granules and studied their morphology using scanning electron microscopy (SEM). The authors also investigated possible interaction between the components using infrared (IR) spectroscopy, differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD).

Materials

Lupin Research Park (Pune, India) provided a gift sample of meloxicam, Glenmark Pharmaceuticals (Nashik, India) supplied myrj-52, and Signet Chemical (Mumbai, India) provided StarLac. Other ingredients were obtained from Merck (Mumbai). All chemicals used were of analytical grade.

Methods

Preparation of the granules. The granules were prepared in the laboratory by adding molten myrj-52 to the physical mixture of the drug and filler. The batch size was 500 g. The granulation process and the formulation were optimized on the basis of preliminary trials. The final formulation contained 10% meloxicam, 25% myrj-52, and 65% StarLac (w/w). The drug and diluent were mixed in the mortar for 15 min. The mixture was then heated to 50 C on a hot plate. Next, molten myrj-52 was added to prepare the granules. The granulation time was 5 min. At the end of the granulation process, granules were cooled at room temperature by spreading them out on trays, collected, and passed through a #40 sieve.

Preparation of the physical mixture. The physical mixture was prepared by mixing meloxicam, myrj-52, and StarLac with a pestle and mortar for 15 min.


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