Investigation of a Novel “Tablets in Capsule” Theophylline Formulation System for Modified Release

Theophylline is a methylxanthine drug used in therapy for respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. A chronotherapeutic approach towards asthma management is particularly important, as bronchial asthma attacks follow circadian rhythms, since they appear more often during the night and/or early in the morning. Many chronotherapeutic studies have shown the benefits of antiasthmatic medication when they are taken at nighttime and the drug is released in specified times, according to the disease pathophysiology, in order to increase the therapeutic effect and help towards patience compliance [1]. Therefore, theophylline was chosen in the present study as a model active pharmaceutical ingredient as the time of drug release after administration requires a modified release formulation. Lopes and his colleagues (2006) demonstrated that the per os administration of controlled release formulations can be classified into two broad categories: Single unit dosage forms, (SUDFs), like tablets and capsules, and multiple unit dosage forms (MUDFs), like granules, pellets or minitablets. MUDFs offer a high control of drug release, because the dose is administered in many single units and is the sum of the drug in each subunit. Advantages of MUDFs include: smaller interand intra-variability, less risk of dose dumping, higher degree of dispersion in the gastrointestinal system, lessening the risk of high local concentrations [2]. Minitablets offer an alternative dosage form for pellets having low porosity, same shape and size, smooth surfaces with small batch-to-batch variability and are easy to produce [3]. On the other hand, formulating MUDFs with minitablets can become a complex and expensive procedure, since the capsule filling is a tedious process and the minitablet production demands extra care and fine adjustments of the instruments used [4]. Additionally, multilayer tablets are usually composed of two, three or more layers, consisting of the same or different substances and/or excipients. The most important reason of multilayer tablet production is the control over the active substance release. Initially, the burst effect can be avoided and the drug’s dissolution and release can be effected by using various polymers; thus various systems for extended, modified, quick/slow, biphasic, or pulsatile release, have been investigated [5]. Dextran and pectin are polymeric excipients, which when in contact with water molecules absorb them, swell and produce a gel layer. This formation can act as a barrier, keeping the active substance entrapped in the system for a period of time allowing control over the drug release profile. Multilayer tableting is a low cost and effective system for a variety of active substances and excipients and can be integrated in minitableting with analogous results, regarding control release. According to the literature, in the large intestine there is a variety of bacteria species producing a plethora of hydrolytic and reductive enzymes, while performing various processes, such as hydrocarbon and protein fermentation. The major energy source, for such anaerobic bacteria, is hydrocarbons, e.g. non-amyloid polysaccharides. In order to mimic the colon micro-environment, while studying drug release Volume 5 Issue 2 2017