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International Journal of Medical Sciences and Pharma Research 

Open Access to Medical and Research

Copyright   © 2022 The  Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

Process Validation of Solid Antioxidant Skin Supplement Tablets

Sandeep Kumar ¹*, Neetesh Kumar Jain², Apoorva Tiwari¹, Supriya  Shidhaye³

¹ Department of Quality Assurance, Faculty of Pharmacy, Oriental University Indore-India

² Department of Pharmacology, Faculty of Pharmacy, Oriental University Indore-India

³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Oriental University Indore-India

Email: skv_pharma@yahoo.com

INTRODUCTION:

A tablet comes under solid dosage forms. The manufacturing of solid dosage forms involves extensive powder handling.¹Tablets are hard, compressed, biconvex solid dosage form they contain one or more medicament with excipients (Binders, Glidants, Disintegrating agents, diluents and organoleptics etc.

A series of unit operation are involved in manufacturing of tablet which include powder blending for content uniformity and converted into solid mass form either through wet granulation or direct compression. Various unit operation are used which include weighing, sieving, dry mixing/blending, wet mixing drying milling and sieving, blending, compression coating and packing.¹

An antioxidant are compound of many different chemical forms and that inhibit the oxidation of other molecules and delays or prevent to oxidative damage.5Antioxidants are naturally occurring plant substances that protect the body from damage caused by harmful molecules called free radicals.² Antioxidants help prevent oxidation, which can cause damage to cells and may contribute to aging. They may improve immune function and perhaps lower the risk for infection, cardiovascular disease, and cancer. Antioxidants exist as vitamins, minerals and other compounds in foods. A diet containing plenty of fruits and vegetables, whole grains and nuts can supply all the antioxidants your body needs. Diets rich in antioxidants can be very beneficial.³

Validation is the process of establishing documentary evidence demonstrating that a procedure, process, or activity carried out in testing and then production maintains the desired level of compliance at all stages. The purpose of setting validation parameter is to monitor the online and offline performance of the manufacturing process and here validate it. Validation is essential part of Good manufacturing practices .it is therefore, an element of the quality assurance programmers associated with the particular product or process. Validation is concept that has involved in United stated in 1978.The concept of validation has expended through the year to embrace a wide range of activities from analytical methods used in quality control of drug substance and drug product to computerized system for clinical trials, labeling or process control.

In all stages of the product lifecycle, good project management and good archiving that capture scientific knowledge will make the process validation program more effective and efficient. The following practices should ensure uniform collection and assessment of information about the process and enhance the accessibility of such information later in the product lifecycle.

MATERIALS AND METHODS:

Weighing of Excipients and API: For weighing and dispensing clean container is want and the area in which process is done is known as weighing room, central weigh for weighing of Excipients Weighing balance apparatus is use.

Sifting or Milling: Sifting mechanical shifter is use.

Sieving: For sieving #20 and #40 sieve. Sieve is fitted in mechanical shifter.

Dry Mixing: The mixing and blending is occur during tablet manufacturing process and for uniform distribution of material Rapid mixer granulator is used. And also items are considered for mixing: Mixing or blending technique, mixing or bleeding speed, drug uniformity and Excipients uniformity. The following physical properties of drug and Excipients are creating a uniform mix and blend: Bulk density, water content, Surface area of particle, Particle shape and size.

The API Reduced L-Glutathione, Pycnogenol, Alpha Lipoic Acid , Vitamin C Coated , Grape Seed Extract and Excipients Dibasic calcium phosphate, Lactose, Sodium methyl paraben, Sodium propyl paraben, Sodium starch glycolate, Cross Carmellose sodium are loaded in RMG.

Slugging: The Excipients powder put in Slugging machine and powder are formed in ribbon.

Sifting: Mechanical sifter equipped with milled granules in #20sieves. Multi mill equipped and milling is used to break up the lumps and enhance the drying of granulation. Such factors are consider in milling: Mill type, screen size, mill speed, feed rate.

Pre-lubrication & Lubrication: For lubrication bender is use. The percentage of mixing of lubricating agent in a control manner because it also have critical and create defects in tablet like when the ratio of lubricating agent is low it cause such type of problems: Picking, Sticking, Capping, Binding in the die cavity and the ratio is high it cause hardness of tablet is decrease, compression of tablets is not proper, disintegration times of tablet is increase (DTs), dissolution is also decrease and it also affect other property of tablet. PVP K-30, Starch, Aerosil, Talcum powder, Magnesium stearate, Sodium lauryl sulphate are placed in blender.

Compression: Compression to be carried not as per batch manufacturing record using

8.0 mm normal concave plain lower and upper punches and 8.0 mm dies. Set the machine at three different speeds of 15, 25 & 35 RPM. Set the compression machine at desired parameter and collect the sample for pre- compression studies. Set the compression machine at lower and higher thickness and collect samples for dissolution. Divide the total compression time into three equal cycles. Run the compression machine at three different speeds in three cycles respectively and withdraw samples for content uniformity, dissolution and impurity at each speed. And check the physical parameters at each speed.

Dissolution profile: Check the dissolution profile on 12 tablets at 15 min, 20 min, 30 min, 45 min, and 60 min from the pooled sample after the completion of film coating.

SAMPLING LOCATION IN COATING PAN:

Coating was carried as per BMR. Before starting coating, average weight of core tablets was recorded. After coating process the appearance and weight gain during coating was tested. After completion of coating check for Description, Weight variation of 20 tablets, LOD and Weight buildup.

1. After loading the pan with tablets, it is rotated for 1 minute for de-dusting and pre heating of tablets.
2. Inlet air temperature: 50 - 60ºc
3. Outlet air temperature: 45 - 50ºC
4. Atomization air pressure: 3.0 - 5.0 kg/cm2
5. Pan RPM: 3-5
6. Spray gun distance: 20 - 26 cm
7. Spray rate: 40 - 60 ml/gun/min

 Fig. No. 1 Sampling location in Coating Pan

Table No. 1: In-Process Specification (Dry mixing):

Table No. 2: In-Process Specification (Core Tablets):

Table No. 3: In-Process Specification (Coated Tablets):

Table No. 4: Sampling and IPQC plan:

RESULT AND DISCUSSION:

Table No. 5: Observation of Dry Mixing process

Fig No. 2: Graph of batch no. 1. content of dry mixing (10 minutes)

Fig No. 3: Graph of batch no. 2. content of dry mixing (15 minutes)

Fig No. 4: Graph of batch no. 3. content of dry mixing (20 minutes)

Observations: It is observed from the compiled analytical data of the content uniformity and it’s after 5 minutes dry mix the values of the three batches are well within the acceptance criteria as per specifications. The distribution of API is well acceptable at 5 minutes of dry mixing as shown by the samples analyzed data. The results show closer   homogeneity   of    drug distribution in the dry mix stage.

SLUGGING:

1. Temperature and relative humidity of room were 27 ºC and 54 % respectively.
2. Binder solution preparation sufficient quantity of water was added and mixed slowly. And powder was formed in ribbon.

Table No. 6: Observation of Loss on drying at slugging process

GRANULE SIFTING:

20# sieve was used. No damage of sieve was observed.

Integrity of the sieve before and after was found intact.

LUBRICATION:

Temperature and relative humidity were 27 ºC and 54 % respectively.

Direction of knives was clockwise at 10 rpm speed. Lubrication Time was 30 min.

Table No. 7: Observation of Lubrication process

Blend Uniformity and Blending time:

All the results of composite sample for physical parameters were found within the acceptance criteria.

Table No. 8: Observation of Blend Uniformity:

Fig No.5: Graph of blend uniformity at 10 minutes

Fig No.6: Graph of blend uniformity at 20 minutes

Fig No. 7: Graph of blend uniformity at 30 minutes

Table No. 9: Observation of Compression process

CONCLUSION:

The pharmaceutical process validation and process controls are important steps in manufacturing of solid dosage form with consistent to meet the regulatory required standard such as identity, strength, quality, purity and stability in the final solid dosage form tablet. The process validation of Antioxidant tablets for the three batches was conducted for a batch size of 1 lakh tablets at dry mixing, Blending, Compression, Coating and Packing stage. Finished product reports of all the three batches of 01, 02 & 03 shows that final product meets the finished product in-house specifications.

The results demonstrate that the manufacturing process was under control throughout all stage within and between batches. The three validation batches of tablet containing Reduced L- Glutathione, Pycnogenol, Alpha Lipoic Acid, Vitamin C Coated, Grape Seed Extract comply with the approved in-process and finished specifications defined for the product. The overall review of result shows consistency and reproducibility within and between batches.

Hence, it is concluded that the manufacturing process and the equipments adopted were strong enough and produce product meeting pre-determined standards and quality attributes, therefore the process stands validated.

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