EFFECT OF MOISTURE CONTENT OF EXICIPIENT (MICROCRYSTALLINE CELLULOSE) ON DIRECT COMPRESSIBLE SOLID DOSAGE FORMS

EFFECT OF MOISTURE CONTENT OF EXICIPIENT (MICROCRYSTALLINE CELLULOSE) ON DIRECT COMPRESSIBLE SOLID DOSAGE FORMS

Monika Tomar ^*, Singh Ajay Kumar and Sinha Amit Raj

Sigachi^® Industries Private Limited, Dahej SEZ Gujarat, India.

ABSTRACT: Quality of pharmaceutical product is very important because pharmaceuticals drugs should be safe and therapeutically active formulation performance should be consistent and predictable. Final product quality depends on all ingredients which is used for making the final product tablet. Final product tablet is made by the addition of bulk drug and excipients. The continuous evolution of the bulk drugs and excipients can only ensure the quality of final product. Moisture content of API’S and excipients plays a very important role to manufacture the final product. It is may affect the physical and chemical properties of final product. Moisture content affects the physical, chemical and microbiological properties of pharmaceutical finished dosage forms. In direct compression process, high and extra low moisture content could be it affects the hardness of tablet. For satisfactory hardness of tablet, room temperature and humidity must be maintained in a specific limit. Tablet hardness is also most import parameter for any solid dosage form.

Quality parameters, Microcrystalline cellulose, Moisture content, Tablet hardness, Weight variation, Percentage Friability

INTRODUCTION: Quality is the collection of feature and characteristics of a product that contribute to its ability to meet requirements and also creating standards for producing acceptable products. Quality can be defined as the measurement of excellence and significant variations or free from defect deficiencies. Quality is measured by the degree of conformance to predetermined specification and standards. To the ethical pharmaceutical manufacturer it implies a detail system of inspection and control covering the production, evaluation, distribution of every drug bearing the company’s label ^{1, 2}.

It is the purpose of these operations to produce medication of superior efficacy, safety and elegance and to provide assurance to physician, pharmacist and the consumer that the given product performs uniformly and in a manner satisfactory for the purpose for which it is recommended. Quality of a pharmaceutical product i.e. solid dosage form (tablet) can be guaranteed by evaluating different physical, chemical and microbiological test of from raw materials to finished product ^{1, 3}. All parameters of excipients and API’s should lie under limit such as bulk density, particle size and moisture content etc. If moisture content of excipients and API’S are above limit it may effect the physical, chemical and microbiological quality of final product ⁴.

Moisture content plays an important role in final product. Moisture in final product comes from many sources. Moisture may come from the bulk drug or inactive excipients in the formulation.

In pure chemicals, moisture may be present as water of crystallization and/or as adsorbed water. When moisture is above limit, however it may be affecting on stability of product and could increase chances of microbial contamination ⁵. Moisture content affects manufacturing of the solid formulation. Higher moisture content in the powder is not good. It can result in poor powder flow, which could further result in irregular tablet parameter performance ^{4, 5, 6}. It may also result in sticking problems on the surface of the tablet. When moisture is present under limits it helps the API and excipients in binding ⁶. In direct compression formulation, different type of excipients are used i.e. starch, microcrystalline cellulose (MCC), polyethyleneglycol (PEG) and hydroxyproply methyl cellulose (HPMC) ^{7, 8, 9}.

HiCel^TM Microcrystalline cellulose is a common excipient used for tabletting in pharmaceutical industries for wet granulation and direct compression formulations ^{5, 10}. It consists of purified partially de-polymerised cellulose prepared by hydrolyzing dissolving grade wood pulp with mineral acid ^{11, 12}. It exists as partial crystalline regions and serves a number of functions in solid dosage formulations ^{13, 14}.

The moisture content of microcrystalline cellulose is about 4% to 5 % which is good for direct compression formulation, while USP monograph specification limit is not more than 7%. A number of studies have confirmed that higher and extra low moisture content of Microcrystalline Cellulose influence the hardness of direct compressible tablets. We are using Hicel^TM 90M and AceCel^TM 102G Microcrystalline Cellulose for this study.

MATERIAL AND METHOD:

Material: HiCel^TM 90M (Spray Dried Microcrystalline Cellulose) and AceCel^TM 102G (Air Stream dried Microcrystalline Cellulose) were used for manufacturing the tablet direct compression technique. Digital weight balance (Mettler Toledo, Model no. ML802/A01) used for weighting the sample. Hot air oven (Model no. PNX-14) used for testing moisture content.  Proton mini press (model 10 STN “D”) “D” type tooling machine was used for makeing the tablets. Digital tablet hardness taster (Labindia model no.TH1050M) was used for test tablet hardness. Friability test done at Baroda analytical services in Vadodara, Gujarat.

Method:

Moisture content: ^{5, 6, 10} Heat the shallow bottle in a hot air oven (Model no. PNX-14) at 105°C for 30 minutes after that cool it in desiccator at room temperature. Tare weight the Shallow bottle and take about 1 gm of HiCel ^TM MCC in shallow bottle, set oven at 105°C and kept for 3 hours. After 3 hours take out the shallow bottle allow to cool in desiccator at room temperature. When the shallow bottle is cool take weight again, Calculate moisture content by using the following formula.

Moisture content =  ....... (1)

Tablet Compaction: ^{5, 6, 15} Compacts of   ̴ 500 mg tablet were made on 10 station proton mini press (Model no. MINI PRESS 10 “D”) using D tolling dies and punches. Machine operating pressure ranges 10 to 60 KN.

Weight variation of Tablets: ^{14, 15} Random 10 tablets were taken from each batch and each tablet was weighted individually using electronic digital balance (Mettler Toledo, Model No.-MS204S /A01) The average weight of all tablets was calculated following formula (equation 2) The pharmacopeial limit of weight variation is mentioned in  (Table 1) .

 ..... (2)

TABLE 1: WEIGHT VARIATION TEST LIMITS FOR TABLETS (USP)

Hardness of Tablet: ^{15, 16} Random 10 tablets were taken from each batch. Electronic digital hardness test machine (Labindia tablet hardness tester, Model No.-TH1050 M) was used for hardness test. Individually, a tablet was placed between two anvils, force was applied to the anvils, and the crushing strength that just caused the tablet to break was recorded. Finally the reading was taken in kp[kgf] on display of hardness machine.

Friability of Tablet: ¹⁷ At first 10 tablets were taken. The tablets were carefully dusted prior to testing, then the 10 tablets were weighted electronic digital balance (Mettler Toledo, Model no. ML802/A01). Which was considered as the initial reading. After weight the tablets, all the tablets were placed in the drum of friability tester and rotate 100 times at 25 rpm. After 100 revolutions the 10 tablets were removed and re-weighted. This was the final reading. The percentage was calculated by following formula (equation 3). According to USP the tablets should not lose more than 1% of their total weight.

...... (3)

RESULT AND DISCUSSION:                                                                                                                

Moisture Content: Moisture content of both grades (HiCel™ 90M and AceCel™ 102G) of Microcrystalline Cellulose were investigated and summarized in the Table 2.

TABLE 2: MOISTURE CONTENT AND ANGLE OF REPOSE OF HICEL™ 90M AND ACECEL™ 102G MICROCRYSTALLINE CELLULOSE

Compaction and General Appearances of tablet: Tablets of both grades (HiCel™ 90M and AceCel™ 102G) are ~500mg weight; all tablets are

made at 3.25 tone release pressure, and other related data of tablets mention in Tablet 3.

TABLE 3: GENERAL APPEARANCES OF TABLET

Weight variation of Tablet: All the tablets of both grades are passed in uniformity weight test, i.e. weight variation was found within the pharmacopeial limit shown in Table 4 and 5, and Fig.1 and 2.

TABLE 4: WEIGHT VARIATION OF HICEL^TM  90M TABLETS AT DIFFERENT MOISTURE CONTENT

TABLE 5: WEIGHT VARIATION OF ACECEL^TM 102 G TABLETS AT DIFFERENT MOISTURE CONTENT

FIG.1: WEIGHT VARIATION OF HICEL™ 90 M TABLETS AT DIFFERENT MOISTURE CONTENT WITH MINIMUM AND MAXIMUM PHARMACOPEIAL LIMIT

FIG.2: WEIGHT VARIATION OF ACECEL™ 102 G TABLETS AT DIFFERENT MOISTURE CONTENT WITH MINIMUM AND MAXIMUM PHARMACOPEIAL LIMIT

Hardness variation of Tablet: Tablet hardness of both grades are decreasing with increasing the moisture content of both grades of microcrystalline cellulose related details are mentioned in Table 6 and Fig.3.

Note ¹⁸: It is to be noted that atmospheric condition of room i.e. temperature and humididty may affect the tablet hardness. In case may be excerissed to maintain relative humidity (RH) range of 53% and temperature 23±1 ^oC.

TABLE 6: DIFFERENT MOISTURE CONTENT AND AVERAGE HARDNESS OF HICEL™ 90M AND ACECEL^TM 102G TABLETS

FIG.3: AVERAGE HARDNESS OF HICEL™ 90M AND ACECEL™ 102 G TABLETS AT DIFFERENT MOISTURE CONTENT

Friability of Tablet: Friability of both grades tablets of microcrystalline cellulose decreases with decreased tablet hardness and increased moisture

content of HiCel™ 90M and AceCel™ 102G. Investigated data are reported in Table 7 and Fig. 4.

TABLE 7: AVERAGE PERCENTAGE FRIABILITY OF OF HICEL™ 90M AND ACECEL^TM  102G TABLETS AT DIFFERENT MOISTURE CONTENT

FIG. 4: AVERAGE % OF FRIABILITY OF HICEL™ AND ACECEL™ 102 G TABLETS AT DIFFERENT MOISTURE CONTENT WITH MAXIMUM ACCEPTABLE PHARMACOPEIAL LIMIT

Conclusion: The variation of moisture content of microcrystalline cellulose is the quality parameter of product. It affects the quality of final product. In this study a correlation between moisture content and tablet hardness could be found. The hardness of tablet was lower at higher moisture content of both grades (HiCel™ 90M and AceCel™ 102G) of microcrystalline cellulose powder. No significant difference in resultant hardness was found between moisture content 4% and 5%. When Moisture content of HiCel™ 90M and AceCel™ 102G are 4% to 5%, hardness of tablet is high with low percentage of friability.  This study found that high and extra low moisture content affects the tablet hardness and percentage of friability.

ACKNOWLEDGEMENT: The authors are grateful to Sigachi Hyderabad unit for the supply of the different moisture content of AceCel™ 102G MCC Sample, and special thanks to our company Executive Chairman (R.P. Sinha), Mr. Ilyas Patel and Mr. Gaurav Tripathi for experimental facilitation.

CONFLICTS OF INTERESTS: The authors state and confirm no conflict of interests. No direct funding was received for this study.

REFERENCES:

1. Silverstein: Excipient quality and selection: Pharmaceutical technology Europe 2016; 28 (2): 16-20.
2. Parsant, Nadavadekar, Sheeja Koliyote: Co-processed excipient for orally disintegrating dosase form. International Journal of Pharma Research and review 2014; 3(4):95-100.
3. Gerhardt Armin: Moisture effects on solid dosage forms –formulation, processing and stability. Journal of GXP Compliance 2009; (1):58-66.
4. Monika Tomar, Ajay Kumar Singh and Amit Raj Sinha: Physicochemical parameter of microcrystalline cellulose and the most acceptability in pharmaceutical Industries. Journal of Innovations in Pharaceuticals and biological Sciences 2015; 2(4):570-578.
5. Monika Tomar, Ajay Kumar Singh and Amit Raj Sinha: Powder and tablet profile of microcrystalline cellulose (MCC) of different with degree of polymerization. International Journal of recent scientific research 2016; 7(6):12044-12047.
6. Ahlneck and G. Zografi: The molecular basis of moisture effects on the physical and chemical stability of drugs in the solid state. International Journal of Pharmacy 2004; 62:87-95.
7. Christensen H., Johansen H.E. and Schaefer: Moisture activated dry granulation in a high shear mixture. Drug Devlopment and Industrial Pharmacy 2008; 14:2195-2213.
8. Gregory Thoorens, Fabrice Krier, Bruno Leclercq, Brain Calin and Brigitte Evard: Microcrystalline Cellulose, a direct compression binder in a quality by design environment-A review. International Journal of Pharmaceutics 2014; 473(1-2):64-72.
9. Anna Penkina, Osmo Antikainen, maija Hakola Sirpa Vuorinen, Timorepo, Jouko Yliruusi Peep Veski, Karin Kogermannn and Jyrki Heinamaki: Direct compression of cellulose and lignin isolated by a new catalytic treatment. Journal of AAPS PharmaSciTech 2013; 14(3):1129-1136.
10. Alfonso R Gennaro: Remington-The Science and Practices of Pharmacy. Lippinocott Williams & Wilkins, twenty edition 2001.
11. Liliana A., Mlinea, M. Rajendra, M. Kallam, James A., Farina and Deorkar Nandu: Evaluation and characteristics of a new direct compression performance excipient 2011; 3:1-8.
12. Shlieout G., Arnold K. and Muller G.: Powder and Mechnical properties of microcrystalline cellulose with different degree of polymerization 2002; 3:1-10.
13. United State Pharmacopeia 38: NF33 2015; 6596-6597.
14. Martin Alfred: Physical Pharmacy. B.I. Waverey, sixth edition 2011.
15. Lachman: The Theory and Practice of Industrial Pharmacy. Varghese Publishing House, Third edition 1987.
16. Soppela Ira, Airaksinen Sari, Motti Murtoma, Tenho Mikko, Hatara Juha, Raikkanen Heikki, Y. Jouko, S. Niklas: Investigation of powder flow behavious of binary mixture of microcrystalline cellulose & paracetamol. International Journal of recent science of research 2015; 2(5):1123-1125.
17. United State Pharmacopeia 39: NF34.
18. Horhata ST, Burgio J, Lonski L and Rhodesb CT: Effect of storage at specified temperature and humidity on properties of the direct compressible tablet formulation. Journal of pharmaceutical Science 2012; 5(12):1746-1749.

How to cite this article:

Monika T, Kumar SA and Raj SA: Effect of moisture content of exicipient (microcrystalline cellulose) on direct compressible solid dosage forms. Int J Pharm Sci Res 2017; 8(1): 282-88.doi: 10.13040/IJPSR.0975-8232.8(1).282-88.

All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.