Continuous Tablet Manufacturing Process: As a Part of Lean Thinking

 

Tushar M. Patel¹*, Dr. Mukesh C. Gohel², Dr. A. Ramkishan³

¹Ph.D. Scholar, Hemchandracharya North Gujarat University, Patan: 384265

¹[L.M. College of Pharmacy, Ahmadabad: 380009, Gujarat, India]

²Ahmedabad University, Navarangpura, Ahmadabad: 380009

³Deputy Drugs Controller (II) I/c, CDSCO, Zonal office: Ahmadabad, India

*Corresponding Author E-mail: tushar_patel684@yahoo.com

 

ABSTRACT:

Lean philosophy is an emerging trend in manufacturing of pharmaceutical dosage forms.  There is cut throat competition between pharmaceutical manufacturers to prepare drug products with superior quality at low cost.  In this paper, lean principle for continuous tablet manufacturing process is discussed. The objective of the proposed manufacturing process is to maximize the production by reducing major types of wastes that absorbs money.  The proposed process and design is compared with the commonly employed pharmaceutical manufacturing scenario. Restructuring of the production areas and equipments to the smallest possible unit is proposed for rapid area clearance by the quality assurance department. The proposed process can be adopted at the pharmaceutical industries for smoother production. An effort has been made in the present work to prevent delay in production.

 

 

INTRODUCTION:

Currently the pharmaceutical companies are facing many production problems such as long queue time, idle time for machines, waste of resources including human hours, etc. Large and medium scale pharmaceutical companies contain three to four granulation areas, in which all the assemblies such as RMG (rapid mixture granulator), fluid bed dryer (FBD), sifter and multimill lie in one area only. As per GMP guideline (1), when a manufacturing area is occupied by one batch, no other batch can enter the same area. Thus when one batch enters the granulation area, no other batch enters the same area until the first batch takes an exit from it. This creates idle time for all the equipments, as for example, when RMG is handling a batch, at that time FBD, sifter and multimill are idle. When FBD is handling a batch, at that time RMG, sifter and multi-mill are idle. After completion of lubrication process, the batch has to wait in quarantine till its turn comes for compression. This lead time varies from hours to days depending on the management of the process.

 

This situation requires improvement in manufacturing process which minimizes the idle time of machines, utilizing resources effectively including human hours, minimum waiting time for the next step of the process, etc. Lean thinking can help us to solve this issue. Lean means minimization of waste and getting maximum use of resources. Most business processes are 90 % waste and 10 % value added.  As a part of lean thinking, we have discussed here the idea of continuous pharmaceutical manufacturing system for single high running tablet dosage form in an industry.

 

PROPOSED DESIGN:

The layout of manufacturing process and plant design as per the proposed thinking is shown in Figure 1 and 2. The raw material store, granulation area, paste preparation room, drying room (fluid bed dryer - FBD) and lubrication area are constructed under one heating ventilation and air conditioning (HVAC) system. Separate compartments for granulation/sifting, drying/sifting/milling and lubrication are constructed to adopt the principle of cellular manufacturing process. The proposed design is applicable to single product only. This system can be used for multiple products by carrying out cost-benefit analysis in terms of numbers of additional HVAC system, number of air filters, number of air locks, etc.   

 

Figure 1: Layout for a continuous tablet manufacturing process

 

Figure 2: Layout of manufacturing area for single product continuous manufacturing system

 

The average weight of tablet is 500 mg and batch size of 5 Lac tablets (250 Kg). The rotor speed of 45 station double rotary tablet machine is 25 rpm. This may produce around 2250 tablets per minute. Hence, the time required for compression is around 3.7 hr. Separate areas for sifting/granulation, FBD/sifting/milling, lubrication and compression is considered. We can nullify the idle time for all the machines by adopting the concept of continuous processing by keeping above mentioned machines in separate areas, so that, clearance by quality assurance (QA) is obtained rapidly and rapid and efficient cleaning can be carried out.

 

The advantages of separate facilities for each processing step are: rapid cleaning, rapid environmental control, quick area clearance can be obtained by QA, no or less idle time for the machines, effective utilization of human resource and controlled manufacturing process.

 

Table I shows the hypothetical timeline for various manufacturing steps. We will adopt this time line to draw a layout of a continuous manufacturing process which is shown in Fig. 1. The layout of manufacturing area is shown in Figure 2. Table II shows distribution of various batches in various time periods. Table 2 shows that all the manufacturing areas are occupied after 600 minutes of starting the first batch. This type of manufacturing process is called as a cellular manufacturing process which is a part of lean manufacturing process, in which the whole process is divided in small different cells that can be handled rapidly with focused attention. 

 

Comparison of conventional versus continuous manufacturing process is shown in Table 3. It is clearly seen that significantly higher output can be obtained in continuous manufacturing process with less numbers of machines as compared to conventional process. Reducing cycle time to do mission-critical processes, the growth of the industry would be three times and the profit margin will be doubled.

 

Table I: Hypothetical time line for various steps in tablet manufacturing process.

Sr. N:	Process	Actual process time (min)	Cleaning time/Area clearance time (min)	Total time (min)
1	Sifting-Granulation	30	30	60
2	FBD-multi mill	120	60	180
3	Lubrication	30	30	60
4	Compression	222	138  (Includes change parts; waiting time for QC clearance)	360

 

 

Table II: Distribution of batches during various time period. B with number indicates batch number

Time (min)	Sifting/ RMG	FBD/ sifter1	FBD/ sifter2	FBD/ sifter3	Lubrication	C1	C2	C3	C4	C5	C6
0	B 1	-	-	-	-	-	-	-	-	-	-
60	B 2	B 1	-	-	-	-	-	-	-	-	-
120	B 3	B 1	B 2	-	-	-	-	-	-	-	-
180	B 4	B 1	B 2	B 3	-	-	-	-	-	-	-
240	B 5	B 4	B 2	B 3	B 1	-	-	-	-	-	-
300	B 6	B 4	B 5	B 3	B 2	B 1	-	-	-	-	-
360	B 7	B 4	B 5	B 6	B 3	B 1	B 2	-	-	-	-
420	B 8	B 7	B 5	B 6	B 4	B 1	B 2	B 3	-	-	-
480	B 9	B 7	B 8	B 6	B 5	B 1	B 2	B 3	B 4	-	-
540	B 10	B 7	B 8	B 9	B 6	B 1	B 2	B 3	B 4	B 5	-
600	B 11	B 10	B 8	B 9	B 7	B 1	B 2	B 3	B 4	B 5	B 6
660	B 12	B 10	B 11	B 9	B 8	B 7	B 2	B 3	B 4	B 5	B 6
720	B 13	B 10	B 11	B 12	B 9	B 7	B 8	B 3	B 4	B 5	B 6
780	B 14	B 13	B 11	B 12	B 10	B 7	B 8	B 9	B 4	B 5	B 6
840	B 15	B 13	B 14	B 12	B 11	B 7	B 8	B 9	B 10	B 5	B 6
900	B 16	B 13	B 14	B 15	B 12	B 7	B 8	B 9	B 10	B 11	B 6
960	B 17	B 16	B 14	B 15	B 13	B 7	B 8	B 9	B 10	B 11	B 12
1020	B 18	B 16	B 17	B 15	B 14	B 13	B 8	B 9	B 10	B 11	B 12
1080	B 19	B 16	B 17	B 18	B 15	B 13	B 14	B 9	B 10	B 11	B 12
1140	B 20	B 19	B 17	B 18	B 16	B 13	B 14	B 15	B 10	B 11	B 12
1200	B 21	B 19	B 20	B 18	B 17	B 13	B 14	B 15	B 16	B 11	B 12
…………………..CONTINUOUS…………….

 

 

Table III: Comparison of conventional versus continuous manufacturing process

Parameter	Conventional (With 3 granulation room each containing RMG, FBD, mill, sifter in same room)	Lean Manufacturing (Continuous processing) (Number of machines are mentioned in chart)
Granulation/sifting	Only 3 batches per shift	8 batches per shift
Drying and milling	Only 3 batches per shift	7 batches per shift
Lubrication	Maximum 3 batches per shift	5 batches per shift
Compression	Long waiting; Blend has to be stored in quarantine	Minimum 6 compression can be completed per shift at a speed mentioned earlier
Number of machines required	3 RMG 3 sifter 3 FBD 3 sifter/multi mill 3 blender 6 tablet press	1 RMG 1 sifter 3 FBD 3 sifter/multi mill 1 blender 6 tablet press
Numbers of HVAC required	2 (One for pre-compression process and one for compression area)	2 (One for pre-compression process and one for  compression area)
Number of employees	3 persons in each Granulation room (3 X 3 =9) 2 persons for blender 6 person for tablet press Total: 17	2 persons for RMG/sifter 2 persons per FBD/multi mill (2 X 3 = 6) 2 persons for blender 6 persons for tablet press Total: 16

To reap the fullest benefit of the proposed process one must adopt the concepts of quality by design (QBD) to maintain superior quality and the principle of six sigma to tackle the problem of deviations in quality. Process understanding and process control should be strengthened to minimize the process related errors and improve quality. Proper training to personnel can also bring in radical influence on processing, especially minimizing the reworking of batches. Substantial amount of money can be saved and profit can be increased if scientific approach is adopted in pharmaceutical manufacturing. Day to day problems should be solved by adopting fire fighting approach by specially trained thinkers.

 

CONCLUSION:

It can be concluded that continuous manufacturing process as a part of lean thinking can help industry to improve their competitiveness and strength in the market by reducing the manufacturing cost and time and on-time delivery of the products. The cost of waste, rework and non-compliance of a product are chief reasons for higher cost. Process improvements based on lean thinking can lead to profitability. Large orders can be fulfilled in stipulated timeline.

 

REFERENCES:

[1] Code of Federal Regulations, Title 21, Food and Drugs (Government Printing Office, Washington, DC), Part 211

 

 

Received on 11.09.2012       Modified on 21.09.2012

Accepted on 27.09.2012      © RJPT All right reserved