Formulation of modified-release tablets

Formulation of modified-release tablets

A single, joint report is required for thisexperiment.

This experiment is to be fully completed and the report must be submitted by the stated deadline.

 

 

	PrintName	Signature	Peer- group Mark(SP)	Staff Mark for report (MS)	Total
1
Total			100	100	100

 

 

 

DECLARATION

 

I have read the Programme Guidelines and I understand that Plagiarism and Collusionasdefinedintheguideisnotacceptableandmayresultindisciplinary action.

I confirm that the work submitted is my own and that I have not borrowedor copied from other sources withoutacknowledgement.

 

Signed(1):                                                                                                                    _

 

Date:_                                                     

 

 

 

Staff Mark Grid:

 

Component 1	Fill weight calculation			20
	Benefits of DC	15	Limits of DC	15
	Other formulation strategies			20
Component 2	Moisture content	10	Fill weight calculation	20

 

 

Report Mark: _____________ (out of 100)

 

 

Health and Safety Risk Assessment for Laboratory Practical Sessions involving Hazardous Substances

 

Chemicals

 

Please list the material you will be using for the practical class session. For each chemical, you will need to mark the relevant hazards and control measures. Information for each chemical is readily available from a variety of resources, including the following: www.sigmaaldrich.com; www.fishersci.co.uk

 

Simply search for the material/chemical, then click on the SDS (safety data sheet) where you will find all of the information that you need.

 

COSHH Assessment Please mark relevant hazards and control measures with an X

Hazards

How might they cause harm (including routes of exposure)

Control measures

Substance

Volumes used

Corrosive

Irritant

Harmful

Toxic

Carcinogenic

Oxidising

Flammable

Explosive

Environmental

Biological

List how these cause harm and routes of exposure

Fume cupboard

Microbiological safety cabinet

Laboratory coat

Eye protection

Gloves

Respiratory protection

Other /details*

g or L

C

Xi

Xn

T

Car

O

F

Ex

Env

Biol

FC

MSC

Coat

Eyes

Glov

RPE

Ibuprofen

Lactose

EthocelFP7

MagnesiumStearate

HPMC

Starch

 

Add more rows if required

 

 

Experimental Procedure

 

	1. List significant hazards	Biological Hazards: please include details in section 3 including hazard group and routes of transmission Chemicals: please complete section 3  Other significant hazards (e.g. heat, sharps etc): please fill in table below with significant hazards involved in process and the control measures. Hazard            Harm   Control measures
2. List who might be exposed to the hazards(e.g. staff, students, visitors, consider numbers at risk)		Staff/students carrying out the activity Other students/staff in the vicinity Contractors, cleaners, maintenance staff Others, please specify :

 

 

3. Waste Disposal

 

Please provide details on disposal of chemical and/or biological waste including any special requirements.

 

 

4. Emergency procedures

 

Spillages:

 

 

First Aid:

In case of contact with eyes
In case of skin contact
In case of ingestion
In case of inhalation
Special First aid considerations:

 

 

 

 

 

Declaration

 

I confirm that I have fully listed all hazards associated with both chemicals and the experimental procedure; will fully comply with the safety recommendations in this document and I understand that marks will be deducted for non-compliance to any of these safety recommendations.

 

Compiled, Read and Understood by:

 

Name  of Lab worker (please print)	Signature	Date:

 

 

Demonstrator signature

 

Name of Demonstrator (please print)	Signature	Date:

 

 

Objectives

After completion of this experiment, the student must be ableto:

 

1. Explain why it is useful to modify release of drugs from formulations and identify methods for doingso.
2. Manufacture tablets using direct compression and granulation and appreciate the differentrequirements.
3. Investigate the rationale for modifying release and the steps involved in development of a newformulation.

 

 

Introduction

Modified-release formulations are those which have been designed to optimise the release profile and bioavailability of a drug. They can take a number of forms: tablets, capsules, patches, etc. Monolithic matrices are extensively used for the preparation of oral modified-release delivery systems owing to their simplicity and ease of manufacture using conventional processing equipment. Monolithic systems generally comprise dissolved or dispersed drug within a swelling or slowly eroding polymermatrix.

 

There are two components of this practical. Your ability to complete within the session will form part of the laboratory conduct mark for thispractical.

 

In this experiment, you will prepare two tablet formulations of ibuprofen, one involvinggranulationandoneusingdirectcompression.

 

You should look over the slides on Blackboard so you can work out the ‘fillweight’.

 

 

 

Safety

You are reminded that, during these practicals, you will be operating machinery that is potentially dangerous if not used exactly as directed. The following general rules are to be followed, but there is no substitute for commonsense.

 

!    Use no machinery unless you have been given permission by the lecturer or technician in charge of theclass.

!    Take great care when operating the tabletingmachine.

!    The power to the tableting machine must be switched off before any adjustments to the settings on the tableting machine are made; any adjustments must be carried out under strictsupervision.

 

 

Effective time management, safety and tidy working will be included in the laboratory conductmark.

 

Component1

Manufactureofibuprofentabletsbydirectcompression

 

Theformulationbelowissuitableforpreparationbydirectcompression.

 

Component	Quantity(g)	Manufacturer	BatchNumber
Ibuprofen	17.5	–	–
Lactose	24.5	–	–
EthocelFP7	7.0	–	–
MagnesiumStearate	1.0	–	–

 

 

 

1. Weigh the ingredients on an appropriate balance and follow the Standard Operating Procedure (SOP) to produce your powderblend.

 

 

2. Yourtabletseachneedtocontain175mgibuprofen,socalculatethefillweight necessary to provide this drugcontent:

 

Calculations:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Fillweight:                                                                                              (20 marks)

 

3. Clearlylabelthejarwithyour names, formulation identification anddate.

 

 

4. List three reasons why direct compression may be beneficial compared with granulationtechniques.

 

 

 

 

 

 

 

 

 

(15 marks)

5. List three reasons why it may not be possible to prepare tablets usingdirect compression.

 

 

 

 

 

 

 

 

 

 

(15 marks)

6. Whatotherformulationstrategiescouldbeusedtomodifythereleaseandwhat are the advantages with the method you haveused?

 

 

 

 

 

 

 

 

 

 

(20 marks)

 

Component2

Manufactureofibuprofentabletsusingagranulationmethod

 

You are required to prepare a batch of a mixture of ibuprofen, lactose, hydroxypropylmethylcellulose (HPMC) and starch. You will granulate the powderblend into granules using the wet granulation method. The granules will be driedand used in subsequentexperiments.

 

 

1. Granulatethepowderblendintogranulesusingwetgranulation:

 

1. Prepare a 94 g batch, using appropriate quantities of lactose, ibuprofen HPMC andstarch.

 

Thebatchmustcontainthecomponentsinthefollowingproportions:

 

Ibuprofen	Lactose	HPMC	Starch
20	20	4	3

 

 

1. Mix the components using the mixer. If mixing appears unsatisfactory, then continue by hand using aspatula.

 

1. Add sufficient distilled water in stages to wet the powder, with thorough mixing after each addition, until the powder takes on the appearance of breadcrumbs. Record how much water you added. Be careful not to addtoo much water, or the following stages will be extremely difficult. Once sufficient water has been added, the powder will be sufficiently cohesive toformgranules.Youarelookingforbreadcrumbs,notdough!

 

1. Pass the moist mass through a 710 µm aluminium sieve with a plastic spatula, with gentle pressure. This stage will be very difficult if you have added too muchwater.

 

 

2. Dry thegranules:

 

1. Spread the granules thinly on a steel tray, and dry in a hot air oven at 60°C for 30minutes.
2. Re-granulatethegranulesbypassingthrougha1mmsieve.
3. Determine the moisture content of a small sample of your granules (approximately 100 mg) using the Sartorius “Thermo control” infrared moisture balance. The operating instructions are located by the instrument.

 

Moisturecontent

 

 

Initialweight                    _102.1____________

 

 

Dryweight                        _93.42____________

 

 

Loss ondrying(%)           __________________

(10 marks)

 

 

3. The weight of the granules was determined (5 g) and 3% w/w Croscarmellose sodium and 1% w/w magnesiumstearate was added.

 

 

4. Your tablets each need to contain 200 mg ibuprofen, so calculate the mass of your granules required to provide this dose (fill weight). You will need to consider ALL of the components present in yourgranules.

 

 

Calculations:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Fill weight_____________________                                      (20 marks)

 

Note: we will make your tablets to thisweight

 

5. Clearlylabelthejarwithyour names anddate.