Raman mapping to identify dry and wet states of pharmaceutical components in a hydroxypropyl methylcellulose (HPMC) hydrophilic matrix tablet

Transcription

1 Raman mapping to identify dry and wet states of pharmaceutical components in a hydroxypropyl methylcellulose (HPMC) hydrophilic matrix tablet By Yewande Oni Formulation Insights Group School of Pharmacy Supervisors: Dr J. Burley, Dr C. D Melia and Dr A. J Inchley University of Nottingham and Boots Pharmaceuticals 12 September 2012

2 Principles of the hydrophilic matrix Ingestion of tablet Dry core Swelling front Dry core Diffusion front Dry core Gel layer Erosion front Fig 1: Adapted from Alderman, D.A: A Review of cellulose ethers in hydrophilic matrices for oral controlled-release dosage forms, 1984 Fig 2: A diagrammatic cross section through a hydrated hydrophilic matrix according to Colombo et al

3 Hydroxypropyl methylcellulose OR RO O CH 2 OR O O RO CH 2 O OR O OR n R groups: none; OH USP grade 2208 HPMC methoxy; OCH 3 hydroxypropyl; CH 2 CH(CH 3 )OH Methocel K100M

4 Background HPMC is the most widely used industrial standard polymer in controlled release dosage forms Some drugs and salts are known alter the thermogelation temperature of HPMC Drop polymer cloud point

5 Aims and Objectives Aim: Identify Raman shifts or molecular changes within the matrix in the hydrated state with respect to known additives that are known to affect HPMC cloud point Objectives: 1. Establish reference spectra for the individual components of a HPMC matrix 2. Understand the spectral composition in Raman of an HPMC matrix with respect to its hydration state 3. Distinguish individual components within an HPMC matrix, in the dry and hydrated state, using Raman mapping

6 Materials (Formulations) HPMC Matrix Material % w/w HPMC K100M 30 Caffeine 10 Lactose 39.8 MCC 19.7 Magnesium Stearate 0.5 Pure HPMC matrix Material % w/w HPMC K100M 99 Magnesium Stearate 1 Lactose:MCC tablet Material % w/w MCC Lactose Magnesium Stearate 1

7 Methods Matrix manufacture 250mg ±5mg 8mm diameter matrices Direct compression at 240MPa Data collection Raman spectra were collected using a LabRAM HR system (Horiba, Kyoto, Japan) interfaced with an Olympus BX51 optical microscope 785nm laser 300µm aperture hole, acquisition time of 0.25s repeated 5 times The radiation was detected using a charge coupled device (CCD) detector

8 Results: Excipient materials (dry) Caffeine Raman shift cm Microcrystalline cellulose Raman shift cm Lactose Raman shift cm Magnesium stearate Raman shift cm -1

9 Results: HPMC Methocel K100M (dry) OR cm -1 C-C 890cm -1 -COC RO O CH 2 OR OR O O RO CH 2 O OR O n cm -1 C-C cm -1 -CH Raman 1200 shift cm Raman shift cm -1

10 Dry HPMC matrix

11 Raman map of a dry HPMC matrix Raman map of scattering intensity between 1300 and 1350 cm -1

12 Multivariate Curve Resolution A chemometric statistical method Group of techniques (resolve mixtures) Number of constituents Response profile (e.g. spectra) Concentration Disseminates data without reference point

13 HPMC matrix: HPMC Raman shift cm -1

14 Lactose HPMC matrix: Lactose Raman shift cm -1

15 MCC HPMC matrix: Microcrystalline cellulose Raman shift cm -1

16 Caffeine HPMC matrix: Caffeine Raman shift cm -1

17 Hydrated HPMC matrix

18 Results: Pure HPMC matrix (hydrated) Dry HPMC Intensity minutes minutes minutes 0 45 minutes Raman shift cm -1

19 Results: Hydrated Reference materials Lactose MCC Lactose: MCC blend MCC LACTOSE Raman shift cm -1 Dry MCC lactose powder powder minutes post hydration hours post hydration

20 Results: Hydrated HPMC matrix Raman intensity map of a HPMC matrix 8 hours post hydration in deionised water

21 Results: Initial hydration (0 minutes) Raman map of scattering intensity between 1250 and 1350 cm -1 highlighting caffeine at 0 time point

22 Results: Hydration (60 minutes) Raman map of scattering intensity between 1250 and 1350 cm -1 highlighting caffeine at 60 minutes

23 Conclusions MCR is a useful chemometrix tool to process Raman mapping data Raman mapping can be utilised to find the spatial distribution of components in dry HPMC matrices We do not believe at present that we can resolve the spatial distribution in a hydrated HPMC matrix We can identify changes within an hydrating matrix

24 Acknowledgements Boots Pharmaceuticals for funding Supervisors and motivators Dr J. Burley Dr C. Melia Dr A Inchley Anran Hu Dr S Pygall Dr H Williams Thank you for listening

25 Any Questions?