Pharma Engineering: 2020

Saturday, 21 November 2020

Design Calculations of Pitch Blade Turbine

Good Morning Everyone ...!!!

Hope everyone is doing well.

Received a query requesting the detailed design of agitators instead of general design which i've provided earlier.

Today i'm gonna provide some detailed technical notes on designing of pitch blade turbine.

Most of the design equations were derived based on the equipment's GA Drawing and some were gathered from my experience. Let's hope these will help you.

Before that we gonna discuss some key points and significance of using a PBT (Pitch Blade Turbine).

What are the cases to use PBT ?

For less dense and less viscous reaction mass we prefer PBT, the mixing with PBT shall be axial, which will allow the mass to pump from bottom to top uniformly.

For detailed selection of reactor with agitator click here

Will PBT generate top pumping or bottom pumping or both ?

PBT will generate top pumping i.e., lifting mass from bottom to top.

Lets take an example of 100 L SS Reactor with PBT agitator design, in general we consider 80% occupancy for a reactor. Water as medium. Basic dimensions: Internal Dia - 48 cm, Height - 58 cm, Shell thickness - 0.6 cm.

Let's start the design [majority of the design calculations were of thumb rules],

Dish height = 0.2 x inner dia = 0.2 x 48 = 9.6 cm,

Impeller Dia = 40 % sweep = 0.4 x 58 = 19.2 cm,

Blade width = Impeller Dia / 5 = 19.2 / 5 = 3.84 cm,

Blade thickness = Vessel thickness / 2 = 0.6 / 2 = 0.3 cm,

Liquid level = ((((1000 x liquid vol.)-(0.0809 x Inner dia^3))x4) / (3.141 x Inner dia^2)) + Dish heigh = 48.9 cm

Impeller count = Liquid level x density / impeller dia = 48.89 x 1 / 19.2 = 2.54 ~3

Distance between impeller = Impeller Dia = 19.2 cm,

Volume of reactor = (((3.141 x Inner dia^2 x Vessel height)/4)+(0.0809 x Inner dia^3))/1000 = 113.9 Lts,

Tip Speed = 3.141 x 19.2 x 140 / 60 x 100 = 1.41 m/sec,

Distance between reactor bottom and impeller = Liquid height / 7 = 48.9 / 7 = 6.99 cm,

Liquid density = 1000 Kg/m3,

Liquid viscosity = 0.0008 Kg-m/sec,

Reynolds number = RPS x impeller dia ^2 x density / viscosity = 107365,

Power number = 2.5 [As per generic agitator curves],

Power req. for agitation = Np x density x Impeller Dia^5 x RPS^3 = 8.24 W = 0.011 HP,

Transmission losses = 20%,

Gland losses = 10%,

Gear box losses = 10%,

Agitation power required after considering losses = 0.011 x (20+10+10)/100 = 0.015 HP,

Power with 70% efficiency, i.e., 0.015 / 0.7 = 0.022 HP,

/** Mixing dynamics calculation shall be updated in a short time **/

Baffles Design:

Number of baffles = 4 (say)

Baffle width = Internal dia / 12 = 4 cm,

Baffle height = Vessel height x 0.8 = 46.4 cm,

Baffle thickness = 0.5 - 1 cm,

Bottom clearance = Baffle width / 5 = 0.8 cm,

Distance between baffle and shell = Inner dia / 24 = 2 cm.

That's it ....!!!

These are some of the aspects related to design of PBT agitator.

If any queries, feel free to comment / message me ......!!!

Comments are most appreciated .....!!!

Is the design helpful and a simple reference ?

About The Author

Hi! I am Ajay Kumar Kalva, Currently serving as the CEO of this site, a tech geek by passion, and a chemical process engineer by profession, i'm interested in writing articles regarding technology, hacking and pharma technology.
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Wednesday, 18 November 2020

Corrosion Testing & Rate Estimator

Hiii All ......!!!

Tested positive for Covid & back after a gap. Hope everyone is safe and healthy. Today i want to post related to corrosion and testing.

This is going to be a simple post and the corrosion rate estimator shall be included in our android app.

Hope everyone reading this has installed the app, if not get a copy at,

Install by Clicking here

Let's get back into topic, estimating the corrosion rate through testing. Before that lets check out some of the vocabulary and the testing procedure.

What is Corrosion ?

Corrosion is a process where a pure metal will gain a stable form through a chemical reaction, mostly it can be oxidation or forming hydroxides / sulphides. This can be due to environmental effect, incompatibility etc. This will destroy the metal surfaces gradually.

What is the test for corrosion ?

Coupon test.

What is the testing procedure ?

Placing a piece of metal with known dimensions and weight in the medium to which we need to check the compatibility for certain period of time.

Let's start the calculation with some considered / assumed input:

Dimensions be: L - 0.8 cm; B - 0.6 cm; W - 0.6 cm;

Initial weight: 3.000 g, Final weight: 2.975 g;

Testing time: 3 days.

Calculation begins here:

Weight loss per day = (3.000 - 2.975) / 3 = 0.00833 g/day,

Total surface area = 2 x ( (0.8 x 0.6) + (0.6 x 0.6) + (0.6 x 0.8) ) = 2.64 cm2

Total volume = 0.8 x 0.6 x 0.6 = 0.288 cm3

Density = 3.000 / 0.288 = 10.42 g/cm3

Corrosion rate = (Weight loss / day) / (Total surface area x Density) = 0.00833 / (2.64 x 10.42)

= 0.000303 cm/day = 1.11 mm/year

Half of the job is done by now,

Remaining job is interpretation, which can be done based on below tabulation:

< 0.75 mm/year - Acceptable;

0.75 - 1.53 mm/year - Acceptable for short periods

> 1.53 mm/year - Not Acceptable

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Monday, 19 October 2020

Validations & Types in Pharmaceutical Manufacturing

Hiii All ...!!!

After a gap back with a basic post, as i've received some queries about the types of validations, writing it here today.

I think many of the rookie engineers who join pharma will come across this word "Validation", and by the time they would like to change an organisation, the common thing they google is,

"What is Validation ? & What are the types of validations ?".

I know this because i came across this phase once and i tried my best to remember the definitions available on google a lot, but unfortunately i haven't asked this question during interview. Anyhow while trying to remember the definitions, i found it very much difficult as i can't understand those much since by that time i don't have enough experience in validations.

This post is dedicated for those who are in such a phase and searching for some easily understandable relevant content. Let me explain these simply with some example,

So my request for the readers is 'if you really want to understand what these types with some detailed example, please proceed, else if you are interested in only definitions, i'm sorry for making you starve'.

What is meant by Validation ?

Validation is a process of proving the consistency of a procedure i.e., it can be a manufacturing process in pharma industry.

The consistency shall be proved w.r.t. quality that is pre-determined / pre-specified and if the process is a from R&D then it is not mandatory to prove the consistency w.r.t. output quantity.

But if the process is a scale-up from small scale to large scale, then it will be better to prove the consistency w.r.t. quantity too.

What are the stages of Process Validation ?

There will be three stages in Process Validation, i.e.,

1. Process Design,

2. Process Qualification,

3. Continued Process Verification, simply CPV.

Stage - 1: Process Design shall be done in R&D through literature survey and conducting experiments

Stage - 2: Process Qualification is the stage where the reproducibility shall be checked, i.e., simply executing minimum three batches to show the consistency w.r.t. quality.

Stage - 3: Continued process verification, is nothing but study of data and ensuring process is in control.

Now, let me explain the types of validation with an example.

What are the types of Validations ?

There are four types of validations,

1. Prospective Validation,

2. Retrospective Validation,

3. Concurrent Validation,

4. Revalidation.

Prospective Validation: This is first time validation of a intermediate / API before launching into market.

Concurrent Validation: This type of validation is used only for monitoring the critical steps and end product quality. Usually reprocess / rework of a product shall be considered as Concurrent Validation.

Revalidation: The name itself makes some sense as revalidation is performed in case of,

a. Product transfer from plant to plant internally,

b. To check reproducibility periodically,

c. Drastic scale-up / scale-down in batch size,

d. Series of failures reported,

e. Major changes done as a part of improvement.

Retrospective Validation: Retrospective Validation is ensuring consistency through evaluation of data from commercial manufacturing. This is abolished and in-place of the retrospective, currently CPV (Continuous Process Verification) were performed.

Now, let's take an example to understand when these types are really used.

Lets say a product Remedesvir is new molecule which is developed in R&D and the process is completely designed and a set of validations were executed in lab to check the consistency and it is found okay. Now we need to execute in plant scale.

Prospective Validation: For the first time if it is executed in plant scale (Commercial) to prove the consistency w.r.t. quality, then it is said to be Prospective.

Concurrent Validation: Product is commercialised after prospective validation. Some failures were reported in quality and there is a developed reprocess procedure for the material, then we need to validate the reprocess / rework route, then it would be termed as Concurrent Validation.

Revalidation: There is a scale-up from say 20 Kg to 200 Kg, then the scale up ratio is 10, so it have to undergo Revalidation. Or there is some scope for yield / quality improvement and for that we need lot many changes, then we have to go with revalidation to prove the consistency.

Anyhow the scalp ratio will vary from company to company and their predefined SOP's.

Retrospective Validation: This is where many of us might get confused if we lack experience. Lets say Remedesvir product is a commercialised and there were ~30 batches executed and the data of all the batches shall be collected and the various quality parameters shall be compared through graphical representation simply we'll use normalised distribution for these and the graph symmetry shall be observed, if the graph is symmetric then the process is in control.

If there is some skewness observed then it might be attributed by some changes. These variations are classified into two categories i.e., Common Cause Variations & Special Cause Variations.

If there is more skewness, then it means that there is a special cause behind, if there is mild skew , then it might be due to common cause which shall be addressed through continuous improvement.

That's it ....!!

Hope the post is self explanatory and readers won't have any queries further,

If any feel free to contact me / Comment below ....!!

Comments are most appreciated .....!!

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Tuesday, 29 September 2020

Hazards and Mitigations in Fluidised Bed Drying of pharmaceutical products

Hii all ...!!!

Back after some days, hope everyone is fine and safe from Covid - 19.

Here today i thought of discussing some of my thoughts against a query i.e., Handling of FBD & Risks involved and their Mitigation plans.

Basically, everyone is well aware of FBD, which works on the principle of direct contact drying and fluidisation. But there lies some hidden hazards which need to be listed out against our material properties before proceeding for drying.

The advantage in FBD is direct contact heating where the heat transfer will be direct from air to material and also it will act as a humidification process, where the solvent present in the material requires humidity for getting knocked out.

Anyhow, i'll start my discussion.

Risks Elaboration:

The common problems which we'll face in drying of materials in Pharma industry is the material vulnerability to static and combustibility due to its thermal sensitivity.

The material sensitivity can be expressed in its low MIE (Minimum Ignition Energy), higher resistivity, higher shock sensitivity. These three need to be addressed during drying in any of the equipment.

Coming to working principle of FBD, the drying will happen by blowing off the air from atmosphere into the FBD fluidisation chamber through a series of filters followed by material holding bowl further followed by filter bags (Finger bags). Air is the most common source of static.

Most of the Pharmaceutical materials will be having higher resistivity in the range of 10^10 - 10^13 ohm-m, which makes it difficult to dissipate static. Also there will be slight attrition of particles during fluidisation, which might lead to reduction of particle size. The reduction of particle size during fluidisation will lead to enhancement in surface area, the increase in surface area will make the material vulnerable to accumulation of more static on surface.

However as there will be continuity in FBD, there will be static discharge, but the problem is when there is prolonged drying then the enhancing of surface area will continue and the accumulation will increase, but whereas the static dissipation rate will be the same. This will be a high risk in production, which need to be addressed.

Sometimes the above scenario will be different like, as there is static accumulated on the particle surface the particles will tend to agglomerate and make it difficult to drying i.e., for knocking out the solvent entrapped. To address this we engineer might implement milling of material intermittently, but this will again create an additional risk, as handling/milling the material where there is higher static accumulated will be a suicide note, but this will be invisible to all.

Sometimes there will be some hygroscopic materials which shall be handled in FBD and the relative humidity shall be maintained based on the DVS (Dynamic Vapour Sorption) isotherm. Usually lower RH's are preferred for handling hygroscopic materials as there will be low amount of humidity but in the same scenario, the dissipation rate will be low at lower RH's, which need to be noted while selecting the operating RH range.

This is the most common hidden scenario which happens during drying in FBD. And as an engineer we should be in a position to address it and make it safer to the operators.

Mitigation Plans:

For addressing these, i got a set of mitigation plans which would be helpful and might requires some further fine-tune.

Below are the set of mitigation plans:

1. Discharge / dissipation of of accumulated static before loading and before unloading of material using Electro Static discharge guns, Below is the screen of static discharge gun for reference:

This hand held gun will be having a digital display which would be displaying the static

Note: There will be voltage rating for these guns, which need to be selected based on material resistivity.

2. Arranging Multi-channelling earth monitoring system, which will be displaying the connectivity of earthing to whole system (it depends on where we have arranged earthing), and to make it productive we need to arrange interlock system with the air sucking blower, means if any of the connectivity is broken, then the blower should be turn off. As the blower would be the source for fluidisation, which leads to static gain,

3. The finger bags which would be in use should be anti-static (irrespective of MOC),

4. Continuous RH monitoring shall be done inside the chamber,

5. Static discharge activity shall be done at specified intervals, like if the drying is of prolonged hours, consider it as 10 hours, then for every 3 - 4 hours, there should be relaxation and dissipation using discharge guns (earth rods shall be used in absence of static discharge guns),

6. Ionizers shall be implement in the inlet after filters section to de-ionize and remove the static charges,

7. Extension of thermowell would increase the surface area / contact area, which might be effective in removal of accumulated charges,

8. Finally, my own suggestion is to implement a mesh containing huge perforations (without disturbing the fluidisation activity, below is the top view of mesh

Usually during fluidisation the material will be on fluidizing with air, which avoids settling and leads to lack of dissipation, and if the mesh is placed in between the bowl and chamber the material would be fluidising through the mesh (which acts as a material medium), the accumulated states would be discharge immediately and even we can eliminate the intermittent relaxations during drying (if exists).

Below is the location for mesh arrangement (subject section is highlighted in red colour):