WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

SJIF Impact Factor 5.210

Volume 4, Issue 12, 358-373 Review Article ISSN 2278 4357

PROCESS VALIDATION OF ORAL SOLID DOSAGE FORM: TABLET

AN OVERVIEW

Mohammad Zameeruddin, Kale Shweta S.*, Jadhav Suryakant B., Kadam Vaishali S.,
Chaware Swapna S.

SSS Indira College of Pharmacy, Vishnupuri, Nanded, Maharashtra, India.

ABSTRACT
Article Received on
06 Oct 2015, Establishing documented evidence which provides a high degree of
Revised on 27 Oct 2015, assurance that a specific process for manufacturing of tablets will
Accepted on 16 Nov 2015
consistently produce a product meeting its pre-determined
specifications and quality attributes. It mainly involves the steps to be
*Correspondence for followed to evaluate and qualify the acceptability of the manufacturing
Author
process of Tablets. The process is limited to the three batches
Kale Shweta S.
manufactured of specific batch size with specified equipments and
SSS Indira College of
Pharmacy, Vishnupuri, control parameters for Tablets. The results suggest providing
Nanded, Maharashtra, documentary evidence that all the manufactured Tablets were
India. evaluated as per specifications. The steps involved such as Blend
uniformity results between 90% - 110%, compression assay results
between 95%-105% were found within acceptable limits. Other tests related to compression
such as hardness, thickness, disintegration, dissolution and for coatings such as weight gain,
dissolution were found within acceptable limit.

KEYWORDS: Solid dosage form; Validation; Process validation; Tablet.

INTRODUCTION[1]
Quality assurance is a wide-ranging concept covering all matters that individually or
collectively influence the quality of a product. It is the totality of the arrangements made with
the object of ensuring that pharmaceutical products are of the quality required for their
intended use. Quality assurance therefore incorporates GMP and other factors, including
those outside the scope of this guide such as product design and development. The objective
of the design and manufacture of the compressed tablet is to deliver orally the correct amount
of drug in the proper form, over a period of time and in the desired location, and to have its

www.wjpps.com Vol 4, Issue 12, 2015. 358

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

chemical integrity protected to that point. The prime objective of any pharmaceutical plant is
to manufacture products of requisite attribute and quality consistently, at the lowest possible
cost. Numerous features are required to ensure product quality, such as chemical and physical
stability, suitable preservation against microbial contamination if appropriate, uniformity of
dose of drug, acceptability to users including prescriber and patient, as well as suitable
packing, labeling and validation1. It is through careful design and validation of both the
process and process controls that a manufacturer can establish a high degree of confidence
that all manufactured units from successive lots will be acceptable. Successful validation of a
process may reduce the dependence upon intensive in-process and finished product testing.

The system of quality assurance appropriate to the manufacture of pharmaceutical products

should ensure that-
Pharmaceutical products are designed and developed in a way that takes account of the
requirements of GMP and other associated codes such as those of good laboratory
practice (GLP) and good clinical practice (GCP).
Production and control operations are clearly specified in a written form and GMP
requirements are adopted
Managerial responsibilities are clearly specified in job descriptions
Arrangements are made for the manufacture, supply and use of the correct starting and
packaging materials
All necessary controls on starting materials, intermediate products and bulk products and
other in-process controls, calibrations and validations are carried out
The finished product is correctly processed and checked, according to the defined
procedures.
Pharmaceutical products are not sold or supplied before the authorized persons have
certified that each production batch has been produced and controlled in accordance with
the requirements of the marketing authorization and any other regulations relevant to the
production, control and release of pharmaceutical products
Satisfactory arrangements exist to ensure, as far as possible, that the pharmaceutical
products are stored by the manufacturer, distributed and subsequently handled so that
quality is maintained throughout their shelf-life.
There is a procedure for self-inspection and/or quality audit that regularly appraises the
effectiveness and applicability of the quality assurance system.
Deviations are reported, investigated and recorded.

www.wjpps.com Vol 4, Issue 12, 2015. 359

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

There is a system for approving changes that may have an impact on product quality.
Regular evaluations of the quality of pharmaceutical products should be conducted with
the objective of verifying the consistency of the process and ensuring its continuous
improvement.

Terminology of Validation[2, 3,4]

The definitions given in the two regulatory documents may be compared as follows
1] Validation
Establishing documented evidence which provides a high degree of assurance that a specific
process will consistently produce a product meeting its pre-determined specifications and
quality attributes. (FDA)Action of proving in accordance with the principles of Good
Manufacturing Practice that any procedure, process, equipment, material, activity or system
actually leads to the expected results. (EC).

2] Process Validation
The documented evidence that the process operated within established parameters can
perform effectively and reproducibly to produce a medicinal product meeting its
predetermined specifications and quality attributes. (EC).

3] Prospective Validation
Validation conducted prior to the distribution of either a new product, or product made under
a revised manufacturing process, where the revisions may affect the products characteristics.
(FDA) Validation carried out before routine production of products intended for sale. (EC).

4] Concurrent Validation
Validation carried out during routine production of products intended for sale. (EC - not
specifically defined in FDA).

5] Retrospective Validation
Validation of a process for a product already in distribution based upon accumulated
production, testing and control data. (FDA)Validation of a process for a product which has
been marketed based upon accumulated manufacturing, testing and control batch data. (EC).

6] Re-Validation

www.wjpps.com Vol 4, Issue 12, 2015. 360

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

A repeat of the process validation to provide an assurance that changes in the

process/equipment introduced in accordance with change control procedures do not adversely
affect process characteristics and product quality. (EC - not specifically defined in FDA).

7] Cleaning Validation
Cleaning validation is documented evidence that an approved cleaning procedure will
provide equipment that is suitable for processing medicinal products. (EC - not specifically
defined in FDA).

8] Validation Protocol
A written plan stating how validation will be conducted including test parameters, product
characteristics, production equipment and decision points on what constitutes acceptable test
results. (FDA - not specifically defined in EC).

9] Worst Case
A set of conditions encompassing upper and lower processing limits and circumstances
including those within standard operating procedures which pose the greatest chance of
process or product failure when compared to ideal conditions. Such conditions do not
necessarily induce product or process failure. (FDA)A condition or set of conditions
encompassing upper and lower processing limits and circumstances within standard operating
procedures which pose the greatest chance of product or process failure when compared to
ideal conditions. Such conditions do not necessarily induce product or process failure. (EC).

10] Risk Analysis

Method to assess and characterise the critical parameters in the functionality of an equipment
or process. (EC - not specifically defined in FDA).

11] System
A group of equipment with a common purpose. (EC - not specifically defined in FDA).

12] Change Control

A formal system by which qualified representatives of appropriate disciplines review
proposed or actual changes that might affect the validated status of facilities, systems,
equipment or processes. The intent is to determine the need for action that would ensure and
document that the system is maintained in a validated state. (EC - not specifically defined in
FDA).

www.wjpps.com Vol 4, Issue 12, 2015. 361

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

13] Design Qualification (DQ)

The documented verification that the proposed design of the facilities, systems and
equipment is suitable for the intended purpose. (EC - not specifically defined in FDA).

14] Installation Qualification (IQ)

Establishing confidence that process equipment and ancillary systems are capable of
consistently operating within established limits and tolerances. (FDA) The documented
verification that the facilities, systems and equipment as installed or modified complies with
the approved design and the manufacturers recommendations. (EC).

15] Operational Qualification (OQ)

The documented verification that the facilities, systems and equipment, as installed or
modified, perform as intended throughout the anticipated operating ranges. (EC - not
specifically defined in FDA).

16] Performance Qualification (PQ)

The documented verification that the facilities, systems and equipment as connected together
can perform effectively and reproducibly based on the approved process method and product
specification. (EC).

17] Process Performance Qualification

Establishing confidence that the process is effective and reproducible. (FDA).

18] Product Performance Qualification

Establishing confidence through appropriate testing that the finished product produced by a
specified process meets all release requirements for functionality and safety. (FDA - not
specifically defined in EC).

Process Validation[5,6]
Purpose
This guideline outlines general principles that FDA considers to be acceptable elements of
process validation for the preparation of human and animal drug products and medical
devices.
Scope

www.wjpps.com Vol 4, Issue 12, 2015. 362

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

This guideline is issued under Section 10.90 (21 CFR 10.90) and is applicable to the
manufacture of pharmaceuticals and medical devices. It states principles and practices of
general applicability that are not legal requirements but are acceptable to the FDA. This
guideline lists principles and practices which are acceptable to the FDA for the process
validation of drug products and medical devices.

Introduction
Process validation is a requirement of the Current Good Manufacturing Practices Regulations
for Finished Pharmaceuticals 21 CFR Parts 210 and 211 and of the Good Manufacturing
Practice Regulations for Medical Devices 21 CFR Part 820 and therefore, is applicable to the
manufacture of pharmaceuticals and medical devices.

Concepts
Assurance of product quality is derived from careful attention to a number of factors
including selection of quality parts and materials, adequate product and process design,
control of the process and in-process and end-product testing. Routine end-product testing
alone often is not sufficient to assure product quality for several reasons.

The FDA Defines Process Validation

Process validation is establishing documented evidence which provides a high degree of
assurance that a specific process will consistently produce a product meeting its
predetermined specifications and quality characteristics.

Types of Process Validation[7,8]

Prospective Validation
Prospective validation includes those considerations that should be made before an entirely
new product is introduced by a firm or when there is a change in the manufacturing process
which may affect the products characteristics, such as uniformity and identity.

Concurrent Validation
Concurrent validation is carried out during normal production. This method of validation can
only be successful if the development stage has resulted in a proper understanding of the
fundamentals of the process. It is carried out during normal production of products intended
for sale. It should involve close and intensive monitoring of the steps and critical points for at
least first three production scale batches. The in-process control results are used to provide

www.wjpps.com Vol 4, Issue 12, 2015. 363

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

some of the evidence required for validation but these are no substitute for validation.
Validation in the production unit mainly comprises of the determination and evaluation of the
process parameters of the facilities applied for the scale-up to final batch size. The control of
all critical process parameters, the results of the in-process controls, final controls and
stability tests should prove the suitability of the important individual steps of a procedure.

Retrospective Validation
Retrospective validation is only acceptable for well-established processes and will be
inappropriate where there have been recent changes in the composition of the product,
operating procedures or equipment. Validation of such processes should be based on
historical data. The steps involved require the preparation of a specific protocol and the
reporting of the results of the data review, leading to a conclusion and a recommendation.

Revalidation[9]
Facilities, systems, equipment and processes, including cleaning should be periodically
evaluated to confirm that they remain valid. Where no significant changes have been made to
the validated status, a review with evidence that facilities, systems, equipment and processes
meet the prescribed requirements fulfils the need for revalidation.

Table 1: Process Control Parameter.

S. No. Parameter Source
1 Average weight
2 Potency End product testing
3 Content uniformity
4 Dissolution time
5 Blend uniformity
6 Moisture content
7 Weight variation In-process testing
8 Tablet hardness

Pre-Requisites for Successful Validation[10]

Understanding
Communication
Experience
Resources
Budget
Plan
Training

www.wjpps.com Vol 4, Issue 12, 2015. 364

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

Standard Operating Procedures (SOPs)

Quality Control Lab Support
Various Approaches in Process Validation

1. Product/process design and development

2. Qualification of the commercial manufacturing equipment and its process
3. Maintenance of the process in a state of control during routine commercial production.

MANUFACTURING PROCESS
Process evaluation and selection
Mixing or blending
Wet granulation
Prior granulation to have a uniform drug/excipients
After milling the dried granulation to add other excipients
Factors in creating a uniform mix or blend
Bulk density
Particle shape
Particle size distribution
Surface area

Items to be consider
Mixing or blending techniques
Diffusion (tumble)
Convection
Pneumatic (fluid bed)
Drug uniformity
Excipient uniformity
Lubricant
Color
Equipment capacity/load

Wet granulation
Binder addition
Binder concentration

www.wjpps.com Vol 4, Issue 12, 2015. 365

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

Amount of binder solution/granulation solvent

Binder solution/granulation solvent addition rate
Mixing time
Granulation end point

Milling
Mill type
Screen size
Mill speed
Feed rate

Drying
Inlet/outlet temperature
Airflow
Moisture uniformity
Equipment capability/capacity

Tablet compression
Tooling
Shape
Size
Concavity
Compression speed
Compression/ejection force
In-process test
Appearance
Hardness
Tablet weight
Friability
Disintegration
Weight uniformity

Tablet coating

www.wjpps.com Vol 4, Issue 12, 2015. 366

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

Coating purpose
Taste masking
Stability
Controlled release
Product idenification
Safety material handling
Tablet properties
Hardness
Shape
Equipment type
Coater load
Pan speed
Spray guns
Application/spray rate
Tablet flow
Inter/outlet temperature flow
Coating solution
Coating weight
Residual solvent level

In process test
Moisture content of dried granulation
Granulation particle size distribution affects
Tablet compressibility
Hardness
Thickness
Disintegration
Dissolution
Weight variation
Content uniformity
Blend Uniformity
Individual tablet/capsule weight
Tablet hardness
Tablet thickness

www.wjpps.com Vol 4, Issue 12, 2015. 367

 Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

Disintegration

Finished product test

Appearance
Tablet mottling
Picking of the monogram
Tablet filming
Capping of the tablets
Tablet colored
Assay
Content uniformity
Beginning
Middle
End
Tablet hardness
Tablet friability
Dissolution

Table 2: Assessment of Critical Process Parameter.

Process Steps Critical Variables Rational Critical Parameters
-To ensure uniform
1. Particle size - Right sievenumber
Particle size distribution
1. Sifting distribution of - Sieve integritybefore and
of sifted input material
sifted materials after use
Security sifting
- Blending time
- Speed of blender
- Quantity to beblended
To obtain final blend
1. Blending Time - Assay
2. Blending uniformity for
(with lubricant) - Bulk / Tap density
Compression
-Sieve analysis Blend
uniformity
- Water by KF
- M/C Speed
1. Degree of - Average weight
pressure applied To meet the desired - Weight Variation
3.Compression 2. Machine Speed product specification till - Thickness
(300,400 and 500 Compression - Hardness
Tab/Min) - Friability
- DisintegrationTest
1. Pan Speed(RPM) To meet the desired final - RPM of coatingpan
4. Coating
2. Inlet Air temp product specification - Inlet temp.

www.wjpps.com Vol 4, Issue 12, 2015. 368

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

3. Outlet Air temp - Outlet temp.

4. Spray rate - Coating time
5. No of guns used - DissolutionProfile
6. Distanceofcoating - Appearance
guns fromthe bed - Weight build up
7. Pre- Warming - Spray Rate
Coating time
8. Drying Time
9.AtomizingAirPressue

CRITICAL PROCESS PARAMETERS FOR COMMON SOLID DOSAGE FORM

UNIT OPERATION ARE
Blending
Blend time, rotation rate, agitator speed, room temperature, humidity.

Dry granulation (Roller compaction)

Roll speed, feed screw speeds, roll force/pressure, and roll separation/gap, room
temperature/humidity.

Milling
Impeller speed, feed rate, room temp, humidity.

Fluid bed granulation

Granulation fluid mixing time, fluid mixing speed, fluid amount, fluid addition rate, fluid
temperature, spray nozzle air volume, bed mixing time, supply air flow rate, dew point,
product bed temperature, exhaust air temperature, filter shaking intervals.

Compression
Tablet weight, turrent speed, main compression force, pre compression force, feeder speed,
upper punch entry, room temperature, humidity.

Coating
Coating suspension mixing time, mixing speed, amount, spray rate, atomization, pressure,
pan rotation speed, pre heat time, supply air flow rate, temperature, product bed temperature,
exhaust air temperature. Monitoring the state of robustness.

CONCLUSION

www.wjpps.com Vol 4, Issue 12, 2015. 369

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

Nowadays Validation is the art of designing and practicing the designed steps together with
the documentation in pharmaceutical industry. Validation itself does not improve processes
but confirms that the processes have been properly developed and are under control in
achieving, maintaining the quality of the final product. Application of validation principles
will ensure to maintain quality, consistency and reproducibility in product manufacturing
process and safety of the pharmaceutical products required from regulatory agencies across
the world. The multidisciplinary validation team must identify, study the product and process
characteristics and incorporate the important required validation key parameters to ensure
that that product will meet all quality, manufacturing, and regulatory requirements. Process
validation in solid dosage form is a systematic approach in identifying, measuring,
evaluating, documenting and re-evaluating the critical steps in the pharmaceutical solid
dosage form manufacturing process with control to assure consistency in the quality of final
product. From this review we can conclude that 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].

REFERENCES
1. Sharp J. Guide to pharmaceutical manufacturing practice. 3rd ed., Her majestys
stationery office London, 1983; 154-162.
2. Glossary of quality system and development technology. Division of field investigations
office of regional operations, office of regulatory affairs. FDA 1995.
www.fda.gov/gloss.html.
3. Sharp J. Validation How much is required? J Pharm sci and tech, 1995; 49(3): 111-118.
4. Good manufacturing practices for pharmaceutical products: main principles: In WHO
expert committee on specifications for pharmaceutical operations. 37 report, Geneva.
WHO - 2003 (WHO technical report series number 908).
5. Supplementary guidelines on good manufacturing practices: Validation. In WHO expert
committee on specifications for pharmaceutical preparations. 40 report, Geneva. WHO -
2006 (WHO technical report series number 937).
6. A WHO guide to good manufacturing practices (GMP) requirements. Part 2 Validation.
Geneva, global programme for vaccines and immunization WHO-1997.
7. Nash RA. The essential of pharmaceutical validation in pharmaceutical dosage forms:
Tablets. 3rd ed., New York, 1990; 2: 200-259.

www.wjpps.com Vol 4, Issue 12, 2015. 370

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

8. Macormik P, Cullen L. Cleaning validation in pharmaceutical process validation. New

York, 1993; 2: 103-145.
9. Chapman KG, Amer G, Brower G, Green C, Hall WE and Harpaz D. Journal of
Validation Technology, 2000; 6: 505-506.
10. Sharma AA. Review on Process validation of solid dosage form. International Research
journal of pharmacy and science, 2013; 4(2): 80-84.
11. Alam SM. An overview of Pharmaceutical process validation: Journal of Advanced
pharmacy education and research, 2012; 2(4): 185-200.
12. Singh H, Rana AC, Saini S, Singh G. A Review of Industrial process validation of solid
dosage forms. International research journal of pharmacy, 2012; 3(4): 64-75.
13. Iidiko MZ. A Review of Increased importance of the documented development stages in
process validation. Saudi pharmaceutical journal, 2012; 2(3): 111-119.
14. Nandhakumar L,. Dharmamoorthy G,. Rameshkumar S and. Chandrasekaran S. An
Overview of Pharmaceutical validation: Quality Assurance view point. International
Journal of Research in Pharmacy and Chemistry, 2011; 1(4): 1003-1013.
15. Skibsted ET, Boelens HF, Westerhuis JA, Witte DT, Smilde AT. Simple assessment of
homogeneity in pharmaceutical mixing processes using a near-infrared reflectance probe
and control charts. J Pharm Biomed Anal, 2006; 3(2): 200-220.
16. Boehm G, Clark J, Dietrick J, Garcia T. Powder blends and finished dosage units in-
process dosage unit sampling and assessment. J Pharm Sci Tech., 2003; 57: 59-74.
17. Nash R.A., Wachter A.H. Pharmaceutical Process Validation, 3rd Ed. Marcel Dekker,
Inc. New York, 2003; 129: 159-180.
18. Jatto E, Okhamafe AO. An overview of pharmaceutical validation and process controls in
drug development Tropical Journal of Pharmaceutical Research, 2002; 1(2): 115-122.
19. Mergen GJ, Amer G, Angelucci LA, Brower GN. Evaluation and validation of blend
uniformity. Approaches for establishing acceptance criteria, 2001; 7: 100-184.
20. Geoffroy JM, Jimenez P, Mergen G, Muzzio F. The use of stratified sampling of blend
and dosage units to demonstrate adequacy of mix for powder blends. J pharm Tech,
March 2013; 4: 1222-1232.
21. ICH Q7 Harmonised Tripartite Guideline. Good Manufacturing Practice Guide for Active
Pharmaceutical Ingredients, Current Step 4 Version 2000.
22. Sherwood BE, Hunter EA, Staniforth JN. Silicified microcrystalline cellulose (SMCC): a
new class of high functionality binders for direct compression. Pharm Res., 1996; 13(9):
197.

www.wjpps.com Vol 4, Issue 12, 2015. 371

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

23. Edge S, Steele DF, Chen A, et al. The mechanical properties of compacts of
microcrystalline cellulose and silicified microcrystalline cellulose. Int J Pharm., 2000;
200: 67-72.
24. Buckton G, Yoremochi E, Yoon NL, Moffat AC. Water sorption and near IR
spectroscopy to study the differences between microcrystalline cellulose and silicified
miicrocrystalline cellulose after wet granulation. Int J Pharm., 1999; 181: 41-47.
25. Hadgraft J, Ashton P. The effect of sodium lauryl sulfate on topical drug bioavailability. J
Pharm Pharmacol, 1985; 3: 85.
26. Wang LH, Chowhan ZT. Drugexcipient interactions resulting from powder mixing: role
of sodium lauryl sulfate. Int J Pharm., 1990; 60: 61-78.
27. Gissinger D, Stamm A. A comparative evaluation of the properties of some tablet
disintegrants. Drug Dev Ind Pharm., 1980; 6(5): 511536.
28. Gorman EA, Rhodes CT, Rudnic EM. An evaluation of crosscarmellose as a tablet
disintegrant in direct compression systems. Drug Dev Ind Pharm., 1982; 8: 397-410.
29. Gordon MS, Chowhan ZT. The effect of aging on disintegrant efficiency in direct
compression tablets with varied solubility and hygroscopicity. In terms of dissolution.
Drug Dev Ind Pharm., 1990; 16: 437-447.
30. Lerk CF, Bolhuis GK, Smedema SS. Interaction of lubricants and colloidal silica during
mixing with excipients I: its effect on tabletting. Pharm Acta Helv., 1977; 52: 33-39.
31. Johansen H, Moller N. Solvent deposition of drugs on excipients II: interpretation of
dissolution, adsorption and absorption characteristics of drugs. Arch Pharm Chem (Sci).,
1977; 5: 33-42.
32. Danish FQ, Parrott EL. Effect of concentration and size of lubricant on flow rate of
granules. J Pharm Sci., 1971; 60: 752-754.
33. Holzer AW, Sjogren J. Evaluation of some lubricants by the comparison of friction
coefficients and tablet properties. Acta Pharm Suec., 1981; 18: 139-148.
34. Chowhan ZT. Role of binders in moisture-induced hardness increase in compressed
tablets and its effect on in vitro disintegration and dissolution. J Pharm Sci., 1980; 69:
1-4.
35. Rowe RC. The adhesion of film coatings to tablet surfaces the effect of some direct
compression excipients and lubricants. J Pharm Pharmacol, 1977; 29: 723-726.
36. Martini LG, Ford JL, Roberts M. The use of hypromellose in oral drug delivery. J Pharm
Pharmacol, 2005; 57: 533-546.

www.wjpps.com Vol 4, Issue 12, 2015. 372

Kale et al. World Journal of Pharmacy and Pharmaceutical Sciences

37. Motoyoshi K, Nozawa S, Yoshimura M, Matsuda K. The safety of propylene glycol and
other humectants. Cosmet Toilet, 1984; 99(10): 83-91.
38. Wells JI, Bhatt DA, Khan KA. Improved wet massed tableting using plasticized binder. J
Pharm Pharmacol, 1982; 34: 46.
39. Rowe RC. Quantitative opacity measurements on tablet film coatings containing titanium
dioxide. Int J Pharm, 1984; 22: 17-23.
40. Brittain HG, Barbera G, DeVincentis J, Newman AW. Titanium dioxide. Analytical
profiles of drug substances and excipients. San Diego: Academic Press., 1992; 21:
659-691.
41. Hsu ER, Gebert MS, Becker NT, Gaertner AL. Effects of plasticizers and titanium
dioxide on the properties of poly(vinyl alcohol) coatings. Pharm Dev Technol, 2001; 6(2):
277-284.
42. Lewis RJ, Dangerous Properties of Industrial Materials. New York: Wiley., 2004; 11:
2148-2149.
43. Luce GT. Disintegration of tablets enteric coated with CAP. Manuf Chem Aerosol News,
1978; 49(7): 50-67.
44. Cockeram HS, Levine SA. The physical and chemical properties of shellac. J Soc Cosmet
Chem., 1961; 12: 316-323.
45. Labhasetwar VD, Puranik PK, Dorle AK. Study of shellac-glycerol esters as anhydrous
binding agents in tablet formulations. Ind J Pharm Sci., 1988; 50: 343-345.
46. Rowe RC. Materials used in the film coating of oral dosage forms. Materials Used in
Pharmaceutical Formulation: Critical Reports on Applied Chemistry, Oxford: Blackwell
Scientific, 1984; 6: 136.
47. Goodhart FW, Harris MR, Murthy KS, Nesbitt RU. An evaluation of aqueous film-
forming dispersions for controlled release. Pharm Technol, 1984; 8(4): 64-71.
48. Smolinske SC. Handbook of Food, Drug, and Cosmetic Excipients. CRC Press., 1992:
295301.
49. Blanchard J. Effect of polyols on interaction of paraben preservatives with polysorbate
80. J Pharm Sci., 1980; 69: 169173.

www.wjpps.com Vol 4, Issue 12, 2015. 373