School of Applied Science Industry Project Proposal AY2013/2014

Project Title

: Granulation using high shear, fluid bed and extrusion spheronization with milled and sieved lactose : Dawn Er (Dr) : Winnie Fannon (Ms) : DBIO DBMS DENV DMTS DPHM Mixed : Formulation and Nutrition Science (FANS)1 New Materials (NM)2 Environment Technology (ENV)3 Not related to any TDC

PI (s) Co-PI (s) Diploma* TDC*

Human Subject Research Project*: Yes/ No [If yes, please submit IRB forms to Ngeoh_Siew_Chin@rp.sg] Collaborator (s) : Meggle Singapore (Pte) Ltd.

Category*: Research Collaboration Project (RCP)4/ Contract Research Project (CRP)5

*Please indicate accordingly

Core competencies: Functional food development and nutritional studies, pharmaceutical formulations and drug delivery systems, Cancer biology and oncology for applications such as Assay systems for bioactive compounds, Assay models for cancer analysis and Analytical Chemistry
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Core competencies: Identification and development of new functionalities for advanced materials and providing solutions for the use of smart materials in biomedical, aerospace, energy, environment, chemical and electronics industries
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Core competencies: Harnessing waste in distributed power generation

An RCP is between 2 or more parties to work together and contribute resources towards a common research inquiry; drawing synergies from one anothers expertise and experiences in specific fields. Typically, collaborators contribute significantly in-kind, in the forms of manpower, specialised expertise, materials, use of existing equipment, etc. Any intellectual property (IP) that arises from the collaboration is expected to be shared jointly between the parties, based on the inventive contributions provided by the parties.
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A CRP is also between 2 or more parties. However, a CRP is specifically applicable when one party, typically an industry partner, is funding ALL costs required to conduct the project AND expects to own ALL IP and reports from the research.

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BACKGROUND (This section provides the background of the collaboration)

Lactose is a widely utilized excipient used in the pharmaceutical industry to manufacture solid dosage forms e.g. tablets, caplets and pellets. Commonly, one of the many upstream processes to manufacture these solid dosage forms is granulation. Granulation involves the agglomeration of individual powder particles to form larger entities. Some reasons why granulation is carried out include improving physical flow of powder mix, reducing dust formation, reducing powder mix segregation and to modify drug release properties. Industry customers use mainly 2 grades of lactose - 200 mesh (milled) and 100 mesh (sieved) lactose. Lactose 200 mesh is typically chosen because it is the cheapest grade whereas Lactose 100 mesh is a popular choice because it is flowable. Apart from these two reasons, customers are not aware of any other possible benefits or disadvantages of these two grades of lactose. The hypothesis of this project is that the choice of lactose should be matched with the appropriate method of granulation, and not ruled solely by cost and lactose flow properties. The objective of this research project is to investigate the impact of milled and sieved lactose on granulation and consequently tableting. 2. SCOPE OF WORK

The scope of work first involves a short literature search on (i) types of granulation process (fluidized bed granulation, high shear granulation and extrusion-spheronization) and (ii) types of lactose (milled lactose, sieved lactose and the available grades for each type) Students will next make granules using the fluidized bed, high shear granulator and extrusion. Granules formed would be characterized using various methods to determine properties such as size, flow and shape. These granules formed would subsequently be tableted and properties of the tablet would be evaluated. Some of properties include disintegration, dissolution, hardness, weight and friability.

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PROJECT SCHEDULE / TIME FRAME AND RESPONSIBILITY MATRIX

Mar 2013 April 2013 May 2013 June 2013 Sep 2013 Oct 2013 Nov 2013 Dec 2013

(This section provides the project schedule; specifically deliverables and timelines for these deliverable. This may be tabulated in the table below for easy reference).Deliverables Literature review Granulation Tabletting Progress/Interim Report Technology/Invention Disclosure (if applicable) Final Report

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In some situations, it may be helpful to designate the party responsible for the specific deliverable. In such a case, please indicate the relevant notation assigned to the party in the relevant matrix (see e.g. in last bottom cell) 4. DELIVERABLES (This section is meant to clearly indicate the deliverables expected from each party. It should also include expectations of the parties, which may not count as project deliverables e.g. provision of specific materials. Should also include reporting requirements) The RP deliverables for this project are: The students will do a literature search on the different granulation processes and types of lactose A progress report to collaborator in the middle of each semester Final report at the end of each semester

The Collaborator deliverables are: Inputs on the research Provision of raw materials from Meggle

Patents Likelihood of Patentable discovery/invention from this research project? (Yes/No) Likelihood of commercialising/licensing the discovery/invention from this research project? (Yes/No)

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INPUTS TO THE PROJECT / RESOURCES (This is a statement of the existing resources and background IP that each party will be putting into the project. If only in terms of cash or incremental resources, then this section is not necessary) Meggle will be contributing ideas and raw materials, and a unique experience for students to work on industry relevant projects. RP will be contributing manpower, equipment, facilities and generic raw materials to the project. RP background IP Dawn Er (Dr) has the expertise in pharmaceutical solid dosage form processing and characterization. Winnie Fannon (Ms) has prior experience in dosage form design and formulation. Collaborators background IP Meggle is a renowned manufacturer of lactose, and produces different grades of lactose for many industry customers. Chua Siang Meng (Dr) has domain expertise in pharmaceutical dosage form processing and formulation.
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FINANCIAL MATTERS Payment schedule to RP (if applicable) Amount to be paid to RP

Date/Event

Estimated project cost payable by RP

The total project cost per team should not exceed $5000 for 2 semesters. For total cost of $3500 and above, please provide additional justifications for approval. Table for Expenditure Breakdown Category Items Consumables Chemicals for analysis: Ethanol Raw Materials for formulation Magnesium stearate Crospovidone Aerosil Others Plastic bags Wax paper Equipment Others Total Cost Justifications (for total cost above $3500 only)

Cost Estimate (per item) $1500

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ADMINISTRATIVE MATTERS Risk assessment: Low if properly trained to use the equipment References: Banks, M., Aulton, M.E., 1991. Fluidised-bed granulation: A chronology. Drug Dev. Ind. Pharm. 17(11), 1437-1463. Amidon, G.E., 1995. Physical and mechanical property characterization of powders. In: Brittain, H.G. (Ed.), Physical characterization of pharmaceutical solids. New York: Marcel Dekker, 281-319.
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Appelgren, C., 1985. Recent advances in granulation technology and equipment. Drug Dev. Ind. Pharm. 11(2-3), 725-741. Bacher, C., Olsen, P.M., Bertelsen, P., Sonnergaard, J.M., 2008. Compressibility and compactibility of granules produced by wet and dry granulation. Int. J. Pharm. 358(1-2), 69-74. Du, J., Hoag, S.W., 2001. The influence of excipients on the stability of moisture sensitive drugs aspirin and niacinamide: Comparison of tablets containing lactose monohydrate with tablets containing anhydrous lactose. Pharm. Dev. Technol. 6(2), 159-166. Gao, J.Z., Jain, A., Motheram, R., Gray, D.B., Hussain, M.A., 2002. Fluid bed granulation of a poorly water soluble, low density, micronized drug: Comparison with high shear granulation. Int. J. Pharm. 237(1-2), 1-14. Gu, L., Liew, C.V., Heng, P.W.S., 2004. Wet spheronization by rotary processing a multistage single-pot process for producing spheroids. Drug Dev. Ind. Pharm. 30(2), 111-123. Horisawa, E., Danjo, K., Sunada, H., 2000. Influence of granulating method on physical and mechanical properties, compression behaviour, and compactibility of lactose and microcrystalline cellulose granules. Drug Dev. Ind. Pharm. 26(6), 583593. Merkku, P., Lindqvist, A., Leviska, K., Yliruusi, J., 1994. Influence of granulation and compression process variables on flow rate of granules and on tablet properties, with special reference to weight variation. Int. J. Pharm. 102(1-3), 117125. Nicklasson, F., Johansson, B., Alderborn, G., 1999. Tabletting behaviour of pellets of a series of porosities a comparison between pellets of two different compositions. Eur. J. Pharm. Sci. 8(1), 11-17. Student allocation numbers (no. of teams): 1 team of 5 students per semester for 2 semesters Project prerequisites: Students who have taken A373 Pharmaceutics and A476 Pharmaceutical Compounding SAS Lab Infrastructure Requirements: a. Proposed lab for the project (Please check with Jeremy Kong if unsure of lab required)

No lab required

Lab required is W52F

b. Major instruments or capability required (Please indicate at the sharepoint link here)

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