Physicochemical and powder characteristics of various citrus pectins and their application for oral pharmaceutical tablets

Accepted Manuscript Title: Physicochemical and powder characteristics of various citrus pectins and their application for oral pharmaceutical tablets Authors: Parichat Chomto, Jurairat Nunthanid PII: DOI: Reference:

S0144-8617(17)30686-0 http://dx.doi.org/doi:10.1016/j.carbpol.2017.06.049 CARP 12437

To appear in: Received date: Revised date: Accepted date:

7-3-2017 16-5-2017 13-6-2017

Please cite this article as: Chomto, Parichat., & Nunthanid, Jurairat., Physicochemical and powder characteristics of various citrus pectins and their application for oral pharmaceutical tablets.Carbohydrate Polymers http://dx.doi.org/10.1016/j.carbpol.2017.06.049 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Physicochemical and powder characteristics of various citrus pectins and their application for oral pharmaceutical tablets Parichat Chomto1, Jurairat Nunthanid*1-2 1

Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom,

73000, Thailand 2

Pharmaceutical Biopolymer Group (PBiG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom,

73000, Thailand *

Author of correspondence

E-mail address, [email protected], Tel. 66-34-255800, Fax. 66-34-255801

Highlights   

-Physicochemical, powder and swelling properties of citrus pectins are studied -Different properties of pectins will affect tablet property and drug release -Various citrus pectins can be applied for oral pharmaceutical tablets

Abstract The physicochemical and powder properties of citrus pectins varying in molecular weight and degree of esterification (DE) were characterized. All the pectins were flake particles with average sizes of around 84-107 µm in diameter. They were amorphous solids and classified as being from slightly to moderately hygroscopic. Pomelo pectin possessed passable to poor flowability while the others were classified as having fair flowability. Heckel’s analysis indicated that all pectins underwent plastic deformation under compression. Pectin with a lower %DE and higher molecular weight produced higher tensile strength tablets. The swelling kinetics of all pectins during the first 4 hours demonstrated Fickian diffusion and the gel erosion in distilled water of higher %DE pectin was slower. Pectins, at 10% w/w in theophylline matrix tablets, provided fast drug release while those at 50% w/w, delayed drug release which reached 97-100% within 6-8 h. 1

Keywords: Physicochemical property; powder property; citrus pectins Chemical compounds studied in this article Pectin (PubChem CID: 441476); Theophylline (PubChem CID: 2153) 1. Introduction Pectin is a negatively charged linear polysaccharide extracted from the cell walls of tomato, sugar beet and apple plants as well as from the peels of citrus fruits such as orange, lemon and lime (Rolin, 1993). Its molecular structure mainly comprises α-(1-4)-D-galacturonic acid with some methyl ester and Lrhamnose groups with an average molecular weight of 50000-150000 daltons. Amidated pectin may be produced by using ammonia to convert some of the carboxyl groups into carboxamide groups in the process of de-esterification (Sinitsya, Čopíková, Prutyanov, Skoblya, & Machovič, 2000; Sriamornsak, 2003; Thakur, Singh, & Handa, 1997). The approximate pK value of pectin is around 3.5. According to their degree of esterification (DE), pectins are divided into two major groups, low (LM-pectins, 20- 40%DE) and high methoxylated pectins (HM-pectins, 60- 75%DE) (Liu, Fishman, Kost & Hicks, 2003; Sinha & Kumria, 2001; Sriamornsak, 2003; Vandamme, Lenourry, Charrueau & Chaumeil, 2002). Presently, oral tablets still account for over 80% of all dosage forms used in humans. Pectin is used for oral drug delivery, including matrix tablets, gel, hydrogels, aerogels, beads, coated and compression coated dosage forms. The gelation of pectin reduces water penetration and controls the drug release from the dosage forms. For colon targeting systems, pectin triggers the drug release as a result of its degradation by pectinolytic enzymes at the colon (Fernandez-Hervas & Fell, 1998; Macleod, Fell, Collett, Sharma, & Smith, 1999; Meshali & Gabr, 1993; Sinha & Kumria, 2001; Sriamornsak, 2003; Sriamornsak & Nunthanid, 1999; Vandamme, Lenourry, Charrueau & Chaumeil, 2002; Veronovski, Tkalec, Knez & Novak, 2014). The swelling and erosion of citrus pectin and their impact on drug release from matrix tablets has 2

been studied (Sriamornsak, Thirawong, Weerapol, Nunthanid, & Sungthongjeen, 2007), however few studies on the fundamental properties of pectin have been reported. A knowledge of the physicochemical and mechanical properties of pharmaceutical powders, such as particle size, salt form, moisture content, physical state, flowability and compaction behavior, is required for a successful tableting process. These properties dictate how formulations will behave under tablet processing. This information is also useful for anticipating unwanted problems with large-scale manufacture such as loss of crushing strength, sticking, picking, capping and lamination (Jain, 1999; Jivraj, Martini, & Thomson, 2000). The aim of the present study was to investigate the physicochemical characteristics and tableting properties of different types of citrus pectin varying in %DE and molecular weight. Their applications for oral pharmaceutical tablets as a diluent in matrix tablets were evaluated. Their swelling behaviors in distilled water were also monitored.

2. Materials and methods 2.1. Materials Citrus pectins varying in molecular weight (number average, Mn) and %DE were gifts from Herbstreith & Fox GmbH (Werder, Germany), i.e. - LM-pectin: CU020 (amidated pectin, 150 kDa, 29%DE) and CU701 (80 kDa, 38%DE) - HM-pectin: CU201 (200kDa, 70%DE). HM-pectin with low Mn, extracted from a different type of citrus plant, a pomelo (Citrus maxima) (PP, 18 kDa, 78%DE) was also used (Chaidedgumjorn et al., 2009; Sotanaphun et al., 2012). Anhydrous theophylline (Batch no. A000725, Jilin Shulan Synthetic Pharmaceutical Co. Ltd, China), -lactose

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monohydrate (Tablettose 80, IN 300200 B 1275, NZMP Ltd., New Zealand) and all other materials were of pharmaceutical grade and used as supplied. 2.2. Physicochemical and powder characterization of citrus pectin 2.2.1. Morphology study Scanning electron photomicrographs of pectin powders were taken at appropriate magnifications using a scanning electron microscope (SEM, model MX 2000, Cam Scan, Cambridge, England). 2.2.2. Particle size and size distribution study The mean particle size of pectin powders was measured using particle analyzers (Coulter, LS 100Q, USA and Horiba, LA-950, Japan) and their size distribution was analyzed using a sieving method.

2.2.3. Thermal behaviors Thermal behaviors of pectin powders were investigated using a differential scanning calorimeter (DSC, Perkin-Elmer, DSC7, USA) at a scanning rate of 5oC/min from 30-300oC under a nitrogen purge, and a thermogravimetric analyzer (TGA7, Perkin-Elmer, USA) at a heating rate of 5oC/min from 26-300oC. 2.2.4. Powder X-ray diffraction (PXRD) study Powder X-ray diffraction patterns of pectin powders were measured using a powder X-ray diffractometer (Bruker AXS, Diffractometer D8, Germany). 2.2.5. Fourier transform infrared (FTIR) spectroscopy The transmission infrared spectra of pectin powders were measured by the KBr pellet method using an FTIR spectrometer (Magna-IR system 750, Nicolet Biomedical Inc., Madison, WI, USA). 2.2.6. Nuclear magnetic resonance (NMR) spectroscopy

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The Carbon-13 NMR spectra of pectin powders were measured using a solid state 13C NMR spectrometer (Bruker, 400 MHz, Switzerland). 2.2.7. Drug-pectin interaction study Interactions between pectin powders and theophylline, a model drug, were screened by DSC measurement of the physical mixtures of pectin and the drug at a 1:1 weight ratio. The heating rate was 5C/min from 0-300oC (DSC 2010, TA Instrument Inc., New Castle, DE, USA). The transmission infrared spectra of the physical mixtures were also measured in the same manner, as already described in section 2.2.5. 2.2.8. Moisture sorption study The moisture sorption isotherms of the pectin powders were studied using a gravimetric method as described in our previous study (Nunthanid et al., 2004). The samples were stored in desiccators filled with different saturated salt solutions and distilled water to produce various %relative humidity conditions (11.3, 32.8, 54.4, 75.3, 84.3, 93.7 and 99.5 %RH) and kept at 25+2C for 48 h before being weighed. 2.2.9. Powder flowability study The flowability of pectin powders was determined by the value of angle of repose, %Carr’s index, Hausner ratio and %porosity. The angle of repose was measured by the fixed-base method. The bulk (bulk) and tapped (tap) densities of pectin powders were measured using a cylinder and the true density (true) was determined using an air pycnometer (Multivolume 1305, Micromeritic Instrument, USA) (Nunthanid et al., 2004; Wells & Aulton, 1988). The value of Carr’s index, Hausner ratio and porosity () were calculated from the equations (1-3), respectively. All experiments were replicated 5 times. Carr’s index

=

(tap-bulk)/tap x 100

Hausner ratio

=

tap/bulk

(1) (2)

5



=

(1-tap/true) x 100

(3)

2.3. Mechanical properties of citrus pectin: Heckel’s analysis and tensile strength Heckel’s analysis is often used to determine the compaction behavior of compact powders. 300 mg pectin samples were compressed into tablets using a hydraulic press (Carver®, model 4350.L, Indiana, USA) and a punch and die set (10 mm in diameter). The compression force was varied from 34 to 412 MPa. The tablet thickness was measured in die (n=3). The relationship between the compact porosity (ln 1/porosity) and the compression pressure (MPa) of the pectin tablets was plotted following the equation below (4), ln 1/[1-D]

=

kP + A

(4),

where D is the relative density of the powder compacted at pressure P and the compact porosity = [1-D]. The mean yield pressure (Py in MPa), defined by 1/k (slope), is a measure of the plasticity of a compressed material (Busignies et al., 2006; Podczeck & Révész, 1993; Zhang, Law & Chakrabarti, 2003). After 1 week’s storage, the tablet hardnesses were measured and the radial tensile strengths of the tablets [tablet hardness/area (N/m2)] were calculated. 2.4. Swelling behaviors of citrus pectin 300 mg pectin samples were compressed into tablets (about 10 mm in diameter) at a fixed compression force using a hydraulic press (Specac, Inc., USA). The real time swelling and erosion behaviors of the tablets in distilled water were observed at ambient temperature (30+2oC) as described in our previous study (Nunthanid et al., 2009). The %swelling in axial and radial directions were calculated and plotted against time. 2.5. Evaluation of theophylline matrix tablets containing citrus pectin

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300 mg matrix tablets, each containing 100 mg of anhydrous theophylline, each type of pectin at 10, 20, 30 and 50% w/w and -lactose monohydrate, were prepared using a hydraulic press and a punch and die set (10 mm in diameter). The compression force was fixed at 275 MPa. The in vitro drug release in distilled water (at 37+5C) was studied using dissolution apparatus II (Phamatest PTWS3C, Germany) (n=6). The amount of drug release was analyzed using a UV spectrometer (Lambda 2, Perkin Elmer, USA) at λ max, 271 nm. Tablets without pectin were also prepared in the same manner and used as control tablets. 3. Results and discussion 3.1. Physicochemical and powder characterization of citrus pectin SEM photomicrographs showed that all pectin types were flake particles with a creamy white to brown color (Fig. 1). Their average particle sizes were around 84-107 m in diameter. The DSC thermograms of all pectin types (Fig. S1a) showed water loss peaks at temperatures of around 30-165oC and the onset of degradation peaks at around 210-227oC. Two steps of weight loss in the TGA thermograms of all pectin types due to dehydration (ΔY values) and polymer degradation were observed (Fig. S1b). The results were in agreement with the DSC results. The initial moisture content of all pectin types was about 9-13%. All pectin types were amorphous solids as demonstrated by the halo patterns of PXRD (Fig. S2).

7

CU701

CU020

200

200 PP

CU201

200 µm

200



Fig. 1. Scanning electron photomicrographs of various citrus pectins The FTIR spectra of all pectin types (Fig. 2) showed broad peaks assigned to free OH stretching at wave numbers around 3445-3455 cm-1. Peaks at 1747-1751 cm-1, assigned to carbonyl stretching of the carboxy methyl ester and free carboxyl groups, were also observed (Fig S3). LM-pectins (CU020 and CU701) were in salt forms according to the peaks at 1615 and 1624 cm-1 assigned to C=O stretching of COO-. Peaks at 1634 cm-1 indicating acid forms were observed in those of HM-pectin (CU201 and PP). The C=O stretching of the amide I band at 1681 cm-1 was observed in the spectrum of the amidated pectin (CU020) (Sinitsya, Čopíková, Prutyanov, Skoblya, & Machovič, 2000).

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The solid-state 13C NMR spectra of all pectin types (Fig. 3) were in close agreement with the computerized simulation spectra of pectins. The resonances around 70-102 ppm were assigned to carbons of galactose units. The signals of methoxy carbons (COOCH3) around 54 ppm of the HM-pectin (CU201 and PP) were stronger than those of the LM-pectin (CU020 and CU701). The chemical shifts at 171-172 ppm in the spectra of CU701, CU201 and PP were assigned to carbonyl carbon of methyl ester (COOCH3). A peak of CO-NH2 (amide I) at 175 ppm overlapping the chemical shift of COOCH3 in the spectrum of LM-amidated pectin (CU020) was also observed. It is imperative that a drug-excipient compatibility study should be initiated at the beginning of a dosage form development program. Often, drug-excipient compatibility testing will identify incompatibilities, such as lactoses and amines (Wirth et al., 1998). The DSC thermograms of the physical mixtures of theophylline and pectin showed shifts in the drug melting peaks from 273oC to 267-271oC which might be due to the interference of the degradation peaks of pectin (Figs. S4-S7). In addition, the FTIR spectra of the physical mixtures showed no change in the peaks of theophylline indicating no interaction between the drug and pectin (Fig. S8). The results from the moisture sorption study indicated that all pectin powders were classified as being slightly to moderately hygroscopic. The moisture uptake of all pectin types at nearly 94% RH was around 24-40%. At 50% RH, the moisture uptake of all pectin types was around 8-9% which was less than those of corn starch, potato starch, rice starch and wheat starch (Wade & Weller, 1994; Wells, 1988). The flowability of powders affects the quality of oral pharmaceutical dosage forms in terms of their weight and content uniformity during the manufacturing process. It helps to select the appropriate excipients and method of preparation, whether it is a direct compression or a wet granulation process. According to the values of angle of repose, Carr’s index and Hausner ratio in Table 1, CU020, CU701 and CU201 possessed fair flowability while PP was classified as having passable to poor flowability (Wells, 1988;

9

Wells & Aulton, 1988). The poor flowability of PP might be due to its plate-like particles. It has been reported that particle shape significantly affects the flow characteristics of a powder and the more spherical the shape is, the better the flowability of the powder becomes (Fu et al., 2012). 3.2. Heckel’s analysis and tensile strength During powder tableting, there are three steps in the compression cycle (or force-displacement curve) of a single material. The first relates to packing rearrangement where particles move within the die cavity to occupy existing void spaces between the particles. The second relates to fragmentation and/or plastic deformation of the particles which depend on the material characteristics, particle size, compaction pressure and compaction speed. The third relates to relaxation or instantaneous elastic recovery when the applied force is released. If the elastic forces exceed the tablet tensile strength, the tablet will fail to retain integrity (Busignies et al., 2006; Jivraj, Martini & Thomson, 2000). According to the Heckel’s plots between the logarithm of the inverse of the compact porosity and the applied pressure, the Py values of all pectin types appeared in the linear zone of the plots, between 34 to 200 MPa as shown in Table 1. It was found that the compaction behavior of all pectin types underwent plastic deformation under compression pressure (Py in die about 47-95 MPa). Various pectins with 560%DE (Py in die around 70-114 MPa) have been previously reported as undergoing plastic deformation (Salbu, Bauer-Brandl & Tho, 2010). It has also been reported that a plastic deforming material is shown by its low mean yield pressure (Py) being less than 80 MPa. Materials with high mean yield pressure (Py around 530 MPa) deformed by fragmentation while the Py value of an intermediate material was around 100 MPa (Busignies et al., 2006; Paronen & Iilla, 1996; Paronen & Juslin, 1983; Podczeck & Révész, 1993; Zhang, Law & Chakrabarti, 2003). The pressure-hardness profiles of all pectin types (Fig. S9) indicated that the radial tensile strength of pectin tablets was increased as the applied force was increased. At an applied force of 412 MPa, the 10

tensile strength of LM-pectin with a high molecular weight produced the hardest compacts, whereas HMpectin with a low molecular weight produced the softest compacts (Table 1). This data was consistent with the Heckel’s analysis. The higher compact hardness of LM-pectin may be attributed to the hydrogen bond formation of carboxylate functionality among its molecular structure. The strong binding properties of plastically deformed cellulose particles and the good compactibility of microcrystalline cellulose due to hydrogen bonding have been reported (Bolhuis & Chowhan, 1996). It has also been observed that pectins with higher molecular weights exhibited higher tensile strengths.

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1

12

3.3. Swelling behaviors of citrus pectins The swelling and erosion behaviors of polymers in oral matrix tablets play an important role in controlling the drug released from the tablets. Figs. 4 and 5 illustrate the swelling behaviors of citrus pectin tablets in distilled water. After exposure to the medium, the swelling front moved “inward” as a result of water penetration into the tablets, while the gel erosion front moved “outward”. As described in our previous study, axial swelling was faster and higher than radial swelling (Nunthanid et al., 2009). Owing to their salt forms, LM-pectin (CU020 and CU701) formed a white creamy gel along both axial and radial directions which was completely dissolved within 12 and 24 h respectively. The dissolution of HM-pectin gel (CU201 and PP) was slower and the gel did not dissolve within 24 h except for the axial swelling of CU201. The swelling of PP gel was the highest because of the rapid gel formation and the slower gel dissolution. During the first 4 hours, the swelling kinetics of all the citrus pectins showed Fickian diffusion since they fitted well with Higuchi’s model (Fig. S10) (r2axial: 0.9878, 0.9405, 0.9723, 09968 and r2radial: 0.9362, 0.9282, 0.9248, 0.9953 for CU020, CU701, CU201 and PP respectively) (Peppas, 1985). It has been suggested that the solvent diffusion rate was slower than the polymer relaxation rate for Fickian diffusion and the polymer would become rubbery (Bajpai, Bajpai, & Shukla, 2001). Afterwards, the erosion and dissolution of pectin gel occurred. It was found that the erosion of HM-pectin gel was slower than the swelling rate. 3.4. Evaluation of theophylline matrix tablets containing citrus pectins Tablet hardness and disintegration of theophylline matrix tablets containing citrus pectins at 10 50% w/w are shown in Table 2. As the amount of pectin was increased, tablet disintegration time was increased while tablet hardness was decreased. The hardness of the tablets containing all types of pectin, except for tablets containing CU701 at 10-30% w/w, was significantly different from that of the controls (p < 0.05). The results were consistent with the Heckel’s analysis and the tensile strength study, especially for

13

tablets containing pectin at 50% w/w when LM-pectins demonstrated higher tensile strength and compacts. At 50% w/w, tablet thickness was also significantly increased.

Data of hardness and thickness: *p > 0.05 and p < 0.05, no asterisks (ANOVA test) The in vitro release of theophylline from the tablets containing pectins at 10, 20, 30 and 50% w/w in distilled water are illustrated in Fig. 6. The swelling behavior of pectins played an important role on the drug release profiles. At 10% w/w, the drug release was the fastest while a delay in release was observed when the amount of pectin was increased. The fast drug release was due to the swelling action of the small amount of pectin which induced tablet disintegration. Sriamornsak et al. (2007) reported that HM-pectin could absorb about 70% of its maximum capacity of water within 20 min and formed an appropriate swelling gel that accelerated tablet disintegration. Faster drug release from the tablets containing CU201 and CU701 was observed. During the first 2 h, the lower %swelling of CU201 and CU701 demonstrated a faster gel dissolution rate than the swelling rate. The dissolution of both polymers could induce capillary action or water uptake through pores that contributed to the disintegration behavior accompanied by the swelling action (Desai, Liew, & Heng, 2016). On the contrary, the drug release from the tablets containing pectins at 50% w/w was slower and reached nearly 100% within 8 h. The delayed release was due to greater gel formation of the higher amount of pectins and the drug release was matrix diffusion controlled (Mamani, Ruiz-Caro & Veiga, 2015). The mechanism of drug release up to 60-70% showed Fickian diffusion and the resulting data fitted into the exponential equation illustrated by the Mt/M∞ versus t1/2 plot and Higuchi’s model (Peppas, 1985; Higuchi, 1961). A linear relationship between Mt/M∞ and t1/2 plot was demonstrated with r2 values of 0.9908, 0.9641, 0.9864 and 0.9920 for the tablets containing CU020, CU701, CU201 and PP respectively (Fig. S11). The drug release from the tablets containing CU020 and PP was rather slower because their %swelling during the first 8 h was higher. The pressure-hardness profiles of all pectin types had no effect on the drug release since increasing the amount of pectin would decrease the tablet hardness. 14

4. Conclusion It was suggested that different sources of citrus plants and processes of preparation provided pectins with different characteristics, and that factors such as molecular weight, %DE, %DA, crystalline structure and the salt or acid forms of different types of pectin could affect the process of oral pharmaceutical tableting, tablet properties and drug release from the tablets. All pectins possessed fair to poor flowability and underwent plastic deformation under compression pressure during tableting. Pectins with lower %DE and higher molecular weights produced tablets with higher tensile strengths, however the pressure-hardness profiles of all types of pectin had no effect on drug release since increasing the amount of pectin decreased the tablet hardness. The use of citrus pectins as a matrix diluent at low concentrations could accelerate drug release, while at high concentrations, especially in the cases of HM-pectin or high MW pectins, drug release could be delayed due to their swelling behavior. The mechanism of drug release up to 60-70% was Fickian diffusion. The results from this study give useful basic information for the application of citrus pectins in the pharmaceutical area. Acknowledgements This work was financially supported by the Silpakorn University Research and Development Institute, under the research program “Production of pectin from pomelo (Citrus maxima) peel and its application in the pharmaceutical industry”. Thanks to Herbstreith & Fox GmbH (Werder, Germany) who kindly donated pectin samples. We also acknowledge Jesada Pangpao, Kanitha Chaiuey, Uraiwan Ponpiriyajit and Benjamas Luangwilai for their laboratory assistance.

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Thakur, B. R., Singh, R. K., & Handa, A. K. (1997). Chemistry and uses of pectin–a review. Critical Reviews in Food Science and Nutrition, 37, 47–73. Vandamme, T.F., Lenourry, A., Charrueau, C. & Chaumeil, J.-C. (2002). The use of polysaccharides to target drugs to the colon. Carbohydrate Polymers, 48, 219-231. Veronovski, A., Tkalec, G., Knez, Ž. & Novak, Z. (2014). Characterisation of biodegradable pectin

aerogels and their potential use as drug carriers. Carbohydrate Polymers, 113, 272-278. Wade, A. & Weller, P.J. (1994). Handbook of Pharmaceutical Excipients. (2nd ed.). London: The Pharmaceutical Press. Wells, J.I. (1988). Pharmaceutical Preformulation: The physicochemical properties of drug substances. New York: John Wiley & Sons, (Chapter 4). Wells, J.I. & Aulton, M.E. (1988). Preformulation. In M.E. Aulton (Ed.), Pharmaceutics: The science of dosage form design (pp. 223-253). Edinburgh:Churchill Livingstone. Wirth, D. D., Baertschi, S. W., Johnson, R. A., Maple, S. R., Miller, M. S., Hallenbeck, D. K. & Gregg, S. M. (1998). Maillard reaction of lactose and fluoxetine hydrochloride, a secondary amine. J. Pharm. Sci. 87, 31-39. Zhang, Y., Law, Y. & Chakrabarti, S. (2003). Physical properties and compact analysis of commonly used direct compression binders. AAPS PharmSciTech, 4(4), 1-11.

19

CU020

1747 161 168 1

Fig. 2. FTIR 344 5

% Transmittance

citrus pectins.

CU701

spectra of various

1624 1748

3455

CU201

163 174 4 7

CU020 344 175.37

PP

CU701 4000 172.1

1634 25.5 1751 3450

3000

2000

1000 25.1

-1

Wavenumbers (cm ) CU201 171.2

PP 171.1

200

160

120

80

40

0

ppm Fig. 3. Solid state 13C-NMR spectra of various citrus pectins.

20

Axial swelling at 2 and 12 h CU020

CU201

CU701

PP

2.5 mm 0h

2h



2h

2h CU701

CU020

2h PP

CU201

Fig. 4. Axial and radial swelling

12 h

behaviors of

12 h

12 h

12 h various

Radial swelling at 2 and 24 h CU020

CU701

CU201

PP

10 mm

0h

2h

2h CU020

2h

2h CU701

PP

CU201

citrus pectins in distilled

24 h

24 h

24 h

water.

21

24 h

Fig. 5. %Swelling of

various citrus pectins in distilled water (n=3).

Cumulative % drug release

120

Control CU020, 10%w/w CU701, 10%w/w CU201, 10%w/w PP, 10%w/w CU020, 20%w/w CU701, 20%w/w CU201, 20%w/w PP, 20%w/w CU020, 30%w/w CU701, 30%w/w CU201, 30%w/w PP, 30%w/w CU020, 50%w/w CU701, 50%w/w CU201, 50%w/w PP, 50%w/w

100 80 60 40 20 0 0.0

2.0

4.0

6.0

8.0

10.0

Time (h) Fig. 6. Drug release profiles of theophylline matrix tablets containing various citrus pectins at 10, 20, 30 and 50% w/w in distilled water (n=6).

Table 1. Powder property of various citrus pectins.

22

Type of

Angle of

Hausner

%Carr’s

pectin

repose (o)

ratio

index

(n=5)

(n=5)

(n=5)

CU020

36.78+1.22

1.16+0.02

CU701

37.22+0.88

CU201 PP

% porosity

Py in die

Tensile strength

(MPa)

(MPa)

(n=5)

(n=3)

(n=3)

14.00+1.37

62.72+0.48

47, r2 0.9864

2.50+0.10

1.17+0.02

14.50+1.43

64.75+0.54

56, r2 0.9893

1.57+0.09

36.04+1.14

1.21+0.02

17.25+1.05

63.95+0.43

76, r2 0.9970

2.02+0.04

52.57+0.49

1.32+0.01

24.21+0.85

54.93+0.41

95, r2 0.9966

0.67+0.03

Table 2. Tablet hardness, thickness and disintegration time of theophylline matrix tablets containing various citrus pectins at 10, 20, 30 and 50% w/w. Type of pectin (%

Hardness (kg),

Thickness (mm),

Disintegration time

w/w)

n=6

n=6

(min), n=6

CU020, 10

7.68+0.18

3.013+0.006*

30.00+0.63

CU020, 20

8.88+0.33

3.052+0.015*

> 30

CU020, 30

8.50+0.10

3.028+0.012*

> 30

CU020, 50

8.81+0.29

CU701, 10

*11.23+0.25

2.993+0.013*

17.50+3.62

CU701, 20

*10.42+0.34

3.031+0.024*

> 30

CU701, 30

*10.34+0.15

3.034+0.012*

> 30

CU701, 50

9.69+1.03

CU201, 10

8.81+0.21

3.014+0.006*

4.02+0.02

CU201, 20

7.77+0.14

3.086+0.011*

> 30

CU201, 30

7.00+0.05

3.084+0.011*

> 30

CU201, 50

6.55+1.33

PP, 10

13.33+1.00

2.978+0.032*

23.28+0.72

PP, 20

6.82+0.36

3.065+0.012*

> 30

PP, 30

5.24+0.33

3.145+0.031*

> 30

PP, 50

3.11+0.15

3.362+0.019

> 30

Control

10.76+0.35

3.041+0.089

> 30

3.195+0.019

3.131+0.018

3.280+0.017

23

> 30

> 30

> 30