Data di Pubblicazione:
2012
Citazione:
Development of a mold for capsule-shaped oral pulsatile delivery devices / L. Zema, G. Loreti, E. Macchi, A. Melocchi, A. Gazzaniga - In: Proceedings of World meeting on pharmaceutics, biopharmaceutics and pharmaceutical technology[s.l] : APV, APGI, A.D.R.I.T.E.L.F., 2012 Mar. (( Intervento presentato al 8. convegno World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology tenutosi a Istanbul nel 2012.
Abstract:
INTRODUCTION
In a recent work, the feasibility of injection-molding (IM) in the preparation of a shell device (ChronocapTM) for oral pulsatile delivery and/or time-dependent colonic release was demonstrated [1]. Capsular devices based on hydroxypropyl cellulose (HPC) showed the ability to delay, both in vitro and in vivo, the release of tracer drug powder as a function of the wall thickness and polymeric composition of the shell [1,2].
The mold prototype used offered several advantages, such as the preparation of matching caps and bodies within a single manufacturing cycle as well as of devices with differing nominal shell thicknesses of the thinner wall areas, e.g. the regions where body and cap were not overlapped because of the locking system. However, some limitations were highlighted with respect to the resulting device, such as the variability in the shell thickness and its poor consistency with the nominal value. Moreover, the rate of production and automation extent of the manufacturing process could be improved.
The aim of the present work was therefore the design of a special mold, dedicated to the production of HPC-based capsules, and the subsequent development of a manufacturing process able to enhance the industrial scalability of this pulsatile delivery device.
EXPERIMENTAL METHODS
Materials -Hydroxypropyl cellulose (HPC, Klucel®LF, Aqualon, US; Eigenmann&Veronelli, I); polyethylene glycol (PEG1500, Clariant Masterbatches, I); acetaminophen (AAP, C.F.M., I).
Rheological characterization -A rotational rheometer (ARES-2K, TA instruments, US) was used both in the temperature range of 180-280°C (gap=1mm; frequency=10rad/s; strain=0,1%; measures after 6min) and in isotherm (time from 0 to 1400sec; frequency=10rad/s; strain=0,2%; measures after 3min).
Injection-molding process -A mixture of HPC 90% and PEG1500 10% was prepared in Turbula (Type T2C, WAB, CH), dried in a ventilated oven for 24 h at 40°C and then transferred into the injection-molding press (Baby Plast mod. 6/10P, Cronoplast E; Rambaldi S.r.l., I). IM process conditions are reported within the Results.
In vitro release test – Each capsule body was manually filled with 80mg of acetaminophen powder, closed with a matching cap an sealed by applying a 3% w/v Klucel®LF aqueous solution to the junction area. A six-position USP34 disintegration apparatus was used; each unit was inserted in a basket-rack assembly (only one tube occupied) moving at 31 cycles/min in separate vessels with 900mL of deionized water (37±5°C) [3]. Fluid samples were assayed spectrophotometrically at 248nm. Lag time, i.e. the time to 10% release, and pulse time, i.e. the time elapsed between 90 and 10% release, were calculated from the release curves (n=6).
RESULTS AND DISCUSSION
An IM capsular shell with thickness of few hundreds µm and length as well as height around 10mm would fall within the definition of micromolded products [4]. Microinjection molding (µIM) is not only a simple scale-down of classical IM but also involves radical changes in machines, mold construction and raw materials. In particular, mold design, formulation development and setup of process parameters (e.g. mold temperature, injection speed and pressure, holding time and pressure) should be carried out concomitantly. However, formulation changes (e.g. percentage of plasticizer) at the current stage of development of the pulsatile delivery capsular device might impair the physical stability, release performance or mechanical characteristics. Therefore, in order to develop a robust manufacturing process, we focused on an in-depth evaluation of thermal, rheological and mechanical characteristics of the HPC-based formulation previously established (90% Klucel®LF and 10% PEG 1500, i.e. reference fo
Tipologia IRIS:
03 - Contributo in volume
Elenco autori:
L. Zema, G. Loreti, E. Macchi, A. Melocchi, A. Gazzaniga
Link alla scheda completa:
Titolo del libro:
Proceedings of World meeting on pharmaceutics, biopharmaceutics and pharmaceutical technology