Investigation of Critical Core Formulation and Process Parameters for Osmotic Pump Oral Drug Delivery

Abstract

Abstract. Push-pull osmotic pump (PPOP) tablets of a practically insoluble model drug were developed and the effect of various formulation and process parameters on tablet performance was evaluated in order to identify critical factors. The formulation factors such as the viscosity grade of polyethylene oxide as the primary polymer as well as the level and location of osmogen within the bilayer tablets led to a difference in performance of osmotic tablets and hence should be critically evaluated in the design of such dosage forms. Modification of granulation process, i.e., the granulating liquid composition or drying method of granules, did not impact the drug release from the osmotic tablets at the evaluated scale of this study. The influence of varying dose and aqueous solubility of other model drugs (i.e., theophylline, acetaminophen, and verapamil HCl) on the developed PPOP template was also investigated. Results showed that irrespective of the perceived complexity of development and manufacturing of osmotic pumps, the osmotic tablets in this study demonstrated a robust and yet flexible platform in accommodating different types of drug candidates, regardless of solubility, for the dose levels below 25% w/w of the pull layer formulation.

Investigation into the Effect of Ethylcellulose Viscosity Variation on the Drug Release of Metoprolol Tartrate and Acetaminophen Extended Release Multiparticulates—Part I

“…For drug layering of metoprolol tartrate (aqueous solubility >500 mg/mL), a drug to binder ratio of 70:30 w/w was used, while for acetaminophen (aqueous solubility 14 mg/mL), a 50:50 w/w drug to binder ratio was used (20,21). Metoprolol tartrate formed a homogeneous drug layering solution due to high aqueous solubility of the drug, while acetaminophen formed a drug layering suspension due to limited aqueous solubility.…”

“…One microliter was extracted from the top layer and injected into the gas chromatograph operating at 200°C with H 2 gas flowing at 40 mL/min and air flowing at 200 mL/min. Ethoxyl results were determined based on ethyl iodide standards prepared and ran in a similar manner described above (21).…”

The Properties of HPMC:PEO Extended Release Hydrophilic Matrices and their Response to Ionic Environments

“…In contrast, the PEO matrix shows: (i) less dimensional changes than HPMC during the first hour of hydration; (ii) Isotropic swelling behaviour; (iii) a more rapid water ingress into the matrix and (iv) the complete dissolution of the matrix at 9 hrs. Features (i) and (ii) reflect the low levels of elastic energy stored during PEO deformation, whereas (iii) and (iv) are consistent with the higher water affinity of PEO [41]. This arises because PEO has no hydrophobic substituents whereas Methocel K100M HPMC (USP type 2208) has 22% methoxyl substitution.…”

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

“…'Tablets in capsule' device preparation: In the present study, flat minitablets 6.5 mm in diameter, were compressed to a hardness of 8-10 kp on a hydraulic press (Carver Inc. model 3393) [2,9,10]. Two different mini-tablets were prepared: a. minitablets consisting of 3 layers, where the 2 outside layers where formed from the excipient (2 x 25 mg of either pectin or dextran) and the middle layer, which was formed from the active drug substance (50 mg of theophylline) (Figure 1a …”

“…During the past few years there is increasing interest on 'tablets in capsule' system formulations with various drug substances [19] have tested, in vitro, 'tablets in capsule' system formulations containing clopidogrel and excipients in various combinations. Other researchers have tested the controlled release of mesalazine from 'tablets in capsule' systems for the targeted release of the drug in the colon area [9,20,21]. 'Tablets in capsule' system formulations have also been tested for biphasic release of one drug substance [20,22,23], or more [24,25].…”