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Serial No ISSN:

Author 1 OBITTE, N. C.

Author 2 CHUKWU, A.

Author 3

Title Dissolution Characteristics of

Theophylline Capsules Containing Tacca Involucrata Starch as Binder

Keywords

Description Dissolution Characteristics of

Theophylline Capsules Containing Tacca Involucrata Starch as Binder

Category Pharmaceutical Sciences

Publisher West African Journal of Pharmacy

Publication Date 2007

Signature

Wesl African Journal of Pharmacy (2007), 20(1), 40-50

CONTAINING TACCA INVOLUCRATA STARCH AS BINDER I

9 . %. N. C. OBllTE AND A. CHUKWU

Depariment of pharmaceutical Technology & lndustriai Pharmacy, Faculty of Pharmaceutical Sciences,

Unlverslty of Nigerla, Nsukka.

- - --

R6sumd Des recherches ont 818 faites sur la dissolution et les caracteristiques de ddsintegrant de differentes granules encapsulees prdparees base de I'amidon de Tacca d'involucrata et trois autres reliures de standard (tragacanthe, cellulose carboxymethylique de sodium (SCMC) et d'amidon de mai's). Aucune capsule n'a devid de la condition requise de B.P qui est de 85-115% du contenu du medicament.

1.7mm a encapsuld des granules contenant I'amidon de 5 ou de 10% Tacca ddsagrdgd avant 30min. Toutes les capsules contenant I'amidon de 10% Tacca et ses melanges de polymbre se son1 dgalement ddsagreges en-dessous de 30min. O.IN HCL le profil de ddgagement des capsules reliure-contenantes de 1.7mm est de I'ordre: >Tragacanthe d'amidon de Tacca.de fdcule de mai's de SCMC>; et pour les capsules trop petites de 0.25mm: tragacanthe de I'amidon SCMC> de Tacca> de fdcule de mais>. L'effet de pH sur le profil de degagement des capsules de 1.7mm contenant I'amidon de 15% Tacca etait de I'ordre : >SIF >SGF = 0. IN HCL; Pour ceux contenant 15% SCMC ou tragacanthe, c'etait O.IN HCL >SIF >SGF. Le degagement du theopylline etait plus rapide des capsules en lots F (1.7mm + 1 .Omm) contenant 15% SCMC ou tragacanthe, que du groupe E (1.7mm + 0.25mm trop petits). Pour de:; capsules contenant 15% Tacca ou fecule de mais, le degagement de drogue dtait plus rapide du groupe E que F. Blendmg d'amidon de Tacca avec la tragacanthe, le SCMC ou la fecule de ma'is n'a produit aucune diminution significative dans le ddgagement de la thdophylline a partir de ses capsules.

., 8'. ABSTRACT I' : he dis&hion and disintegrant characteristics of different sized encapsulated granules prepared with Tacca Inwlucata starch and three other standard binders (tragacanth, sodium carboxymethyl cellulo'se (SCMC) and maize starch) were studied. No capsule deviated from the B.P. requirement of 85-115% of drug content. 1.7mm encapsulated granules containing 5 or I,@% Tacca starch disintegrated before 30min. All the capsules containing 10% Tacca starch and Its polymer blends also disintegpted within 30mins. In O.lN HCL, the release profile of the binder-containing 1.7mm capsules Is of the order: SCMC >maize starch > Tacca starch > tragacanth; for 1 .Omm capsules, maize starch > SCMC > Tacca starch z tragacanth; and for 0.25mm undersize capsules, maize starch > Tacca starch > SCMC > tragacanth. The pH effect on the release profile of 1.7mm capsules containing 15% Tacca starch was of the order: SIF > SGF = 0. IN HCI; for those containing 15% SCMC or tragacanth, it was 0.INHCL > SIF > SGF. The release of theophylline was faster from Batch F (1.7mm + l.Omm) capsules containing 15% SCMC or tragacanth, than from Batch E (1.7mm + O.25mm undersize). For capsules containing 15% TaCca or maize starch, drug release was faster from Batch E than F. Blending of Tacca starch with either tragacanth, SCMC or maize starch did not produce any significant decrease in the release of theophylline from its capsules.

INTRODUCTION The main targets of researchers in pharmaceutical

technology and industrial pharmacy worldwide are to introduce new and betpr excipient /drug raw materials'.But the goal of every production pharmacist is to ensure the manufacture of drugs that would meet their claimed efficacy. slhe undertakes this task by choosing binders and other excipients that will impart into the dosage form ph~sicochemical/techgigal characterigtics that will allow the release of the a~tivdin~redient and its smooth absorption through the GIT membranes into the systemic circulation. The dexterity in achieving this determines much of the pharrnacodynamic and pharmacoklnetic characteristfcs of the drug in the body. This laskol ensuring drug bloavailability

via dissolution rate studies has long been s t ~ d i e d ~ - ~ . Furthermore the goal of many workers in this area has been centred on designing in-vitro tests that could quantitatively predict ranks of performance in vivo4.

Theophylline, the drug studied, is an effective broncho- dilator with moderate aqueous solubility (1 in 20 parts of water) and presents inherent bioequlvalence problem due to the nonreproducible dissolution rate of the drug in the GIT Mid . It is used in treating asthma or obstructive pulmonary disease. Reasonable bronchospasm relief is attained with 7-20pg/ml of Theophylline in serum. The plasma half life of theophylline is within the range ol 1- 13hrs, but In children it Is rapidly eliminated from plasma in certain patients, and as such, maintenance of therapeutic

DISSOLUTION OF THEOPHYLLINE CAPSULES CONTAINING TACCA INVOLUCRATA STARCH

levels in the range of 10-20pgIml is not easy in such people. Therefore Weinberger et aI5-6 have recommended its sustained release dosage forms.

Asthmatlc attacks can be 'life threatening and unprecedented, as such normal release capsules may be administered prior to the sustained release forms or normal release granules co-encapsulated with the sustained release granules. Tacca lnvolucrata starch mucilage was employed in the formulation of theophylline granules as a binder to ascertain its usefulness in facilitating the normal release of theophylline.

MATERIALS The materials used were Hydrochlorlc acid, Sodium

hydtoxide, Lactose (M & B), O.IN Hydrochloric acid, simulated gastric fluid without pepsin (SGF), simulated intestinal fluid without pancreatin (SIF) freshly prepared in our laboratory; tragacanth, sodium carboxymethyl celiulose (Fluka), maize starch (M&B), primogel and theophylline hydrate (Merck).

METHODS : / '

Capsule filling Filling of th~,capsules was done':manually.' Granules

were incrementaljy intiodu,ced,lnto.the capsule shell, covered and the weight read off on an electronic balance (Satorius) until 250mg * 1 .Omg weight was attained. 250 1 .Omg of 1.7mm (Batch A), 1 .Omm (Batch B) and 0.25mm undersize (Batch C) granules were individually encapsulated. Also 125 * 1 .Omg of 1.7mm (Batch A) granules and that of 125 rt l.Omg of 0.25mm.undersize (Batch C) were weighed, mixed, encapsulated and labelled Batch E. Similarly 125 k 1 .Omg of 1.7mm (Batch A) and 125 A 1 ,Omg of l.Omm(Batch 0) granules respectively were weighed, mixed, encapsulated and labelled Batch F.

Uniformity of Content Each of 10 randomly selected capsules was opened

and the content emptied into a glass mortar, and crushed. A lOml volume of 0.1N HCI was added to dissolve the granules. The dispersion was introduced into a lOOml flask and made up to the mark. From this stock 1 ml was withdrawn and lranslerred into another 100ml flask and the latter made up to the 100ml mark. With a 5ml pipette having a plug of cotton wool at its tip, 5ml was pipetted out and the absorbance read on a UV-VS spectrophotometer (Pye Unicam) at 271nm for theophylline.

t

Disintegration Time The B.P. method was used. The time it took 6 capsules

containing Batch A (1.7mm) granules to dismtegrate was determined using a Manesty disintegrating unit in 0.1N HCI at 37 * I0C. ,.+,*i;

- . Dissolution Profile Studies

This experiment was conducted on all five Batches -A, B, C, E and F. A 900 ml volume of 0.1 FJ HCL was the medium used. However, simulated intestinal fluid without pancreatin

(SIF) and simulated gastric fluid without pepsin (SGF) were also employed as additional media. Simulated Gastric Fluid (SGF) was prepared as follows: 42.4ml of concentrated Hydrochloric Acid (36.5%) was &ded to 2L of distilled water, l o g of Sodium Chloride was added and stirred until dissolved. The solution was then made up to 5L Simulated Intestinal Fluid (SIF) was prepared as follows: 409 of Sodium Hydroxide was dissolved in 2L of distilled water. 349 of monobasic potassium phosphate was then added and dissolved with stirring. The solution was then made up to '

5L7. The temperature and speed of rotation were 37 * 10C

and 50 r.p.m, respectively. The capsule was introduced into the basket on the spindle and lowered into the medium, and the equipment switched on. The equipment used was Erweka Dissolution apparatus (DT-D model, W. Germany). Samples of the dissolution medium (10ml) were withdrawn at predetermined time intervals. The equivalent volume was immediately replaced. After appropriate dilution, the absorbance of the withdrawn sample was determined in a uv-vs spectrophotometer (Pye Unicam, England) at 271nm.

Calibration Curve A 100mg% stock solution of theophylline was prepared

in the three media of 0.1N HCI, simulated gastric and intestinal fluids. Various volumes ranging from O.lml to l.Om1 of the stock solution were pipetted into ten different 100 ml flasks and diluted to the 100ml mark. The absorbance of 5 ml of each concentration was determined at 271nm in uv-vs spectrophotometer (Pye Unicam, England). The absorbance values were plotted against the concentrations and the slopes determined. From the calibration curves represented in Figs 1-3 the Lambert Beer's constant K, for theophylline in simulated intestinal fluid, simulated gastric fluid and 0.1 N HCI were 0.570,0.566 and 0.560 respectively.

'

Flg 1: %Released vs Tlme(m1n) for theophylllne cepeules(batch A) contalnlng different

concentrations of Tacca starch

West African Journal of Pharmacy (2007) 20(1)

N. C. OBlllE AND A. CHUKWU I)

Time (mln) Fig 2: %Released vs Time(rnln) for theophylline

capsules(batch 8) contalnln~ differenl concentrations . of Tacca starch.

80 -

70 -

60 -

1 P) - so-

#

30 -

20 -

Flg 4: YO Released vs Tlme(rn1n) for theophylline capsules(batch A) contalnlng different

concentrations of rnalze starch

RESULTS AND DISCUSSION

Unlformlty of content No capsule deviated from the 8. P. requirement of 95-

105% of drug (theophylline) content.

Fig 3: % Released vs Time(m1n) for lheophylline capsules(ba1ch C) containing dillerent concentralions

of Tacca starch

Dlslntegratlon tlme Batch A containing 5 or 10% Tacca or maize starch

disintegrated before 30min, while those containing 15% did not. Capsules containing SCMC or tragacanth only disintegrated at 5% binder concentration. The least disintegration time was recorded by capsules of 0% binder. Granules containing 5% Tacca or make starch as blnder were reported to have higher hardness values than granules containing 5% SCMC or tragacanthe. This dependence of disintegration time on hardness has earlier been reported by Gordon et ale.

The capsules containing polymer, blends, i.e. 10% Tacca starch + SCMC, Tacca starch + tragacanth and Tacca starch + maize starch, all disintegrated at 23.6, 21.0 and 19.5 minutes respectively. For the capsules containing tho two starches it was observed that as the contents diffused from the 1.7mm sizedgranules the matrix structure remained undissolved. The contrary was the case with those of SCMC or tragacanth which were more prone to gellation and erosion. The disintegration times of 20.9 or 28.0min for capsules containing 5% Tacca or maize starch were higher- than those of 5% SCMC or tragacanth, 18.0 or 13.8min. At 10 or 15% binder concentrations, capsules containing SCMC or tragacanth did not disintegrate within 15 or 30 min, probably due to the predominant influence of high gellationlo which were not eroded.



Dlssolutlon profiles: The effect of pH of medium on dissolution of

Theophylline capsules

Effect of 0.1 N HCI The dissolution profiles of capsules containing 5, 10 and

15% concentrations of Tacca starch are shown in Figs 1-3. For the Batch A (1.7mm) granule capsules, the T,,,T,, increased with increase in binder concentration - 14,23; 15,27 and 2137 minutes respectively for 5, 10 and .15% concentrations. For Batch B ( I .Omm) capsules however, there was a small consistent decrease, 29,46; 27,44 and 22,39 minutes respectively. In the case of Batch C (0.25mm) capsules, the release pattern of theophylline was not consistent -17,34; 82,15 and 15,30min respectively. The Batch A capsules had a relatively lower T, (rapid release) values than Batch B. 10% concentration of Batch C capsules gave an unusual prolonged release (T,, 82min) than others. This could probably be due to the maintenance of intact granules (which did not quickly crumble) that would actually provide a small, restricted surface area that would lower the rate of dissolution. However If one considers the above observation from the particle size perspective, it would be contrary to an experimental observationt1 that increasing the surface area by particle size reduction is an acceptable method of increasing dissolution rate.

Dissolution of theophylline (Figs 4-6) from capsules containing maize starch was generally rapid. This can be attributed to the minimal binding and high disintegrant characteristics of maize starch. The T50, T70 are as follows: - for Batch A (1.7mm) capsules: 10,16; l3,27 and 14,37 minutes respectively; for Batch B ( I .Omm) capsules: 14,17; 9,11 and 6,8 minutes respectively; and for Batch C (0.25mm undersize): 3,4; 6,lO; and 9,25 minutes respectively.

Flg 4: % Released va Tlrne(rn1n) for thedphylllne capaulea(batch A) contalnlng different

concentretlone of rnalze atarch


According to the modified Noyes-whitney equationt2 the dissolution rate of a drug from small particles is generally faster than that from large particles, this being due to the fact that dissolution rate depents on the specific area in contact with the dissolution mdtiiurn. This explains the highest T, values of the Batch A (1.7mm) capsules over the batches with smaller granules, The slowest release took place in Batch B capsules containing Tacca starch, while for maize starch, it was in Batch A capsules.

80

2 5 B 13 15 20 30 40 50 60 T l m e (min)

Fig 5: % Released vs Tlme(mln) for theophylllne capsules(ba1ch 6) contalnlng different concentrations

of maize starch

Flg 6: % Releaaed va Tlrne(m1n) for theophylllne capsules(balch C) contalnlng dlfferent

concentratlona of rnalze starch

N. C. OBITTE AND A. CHUKWU

The release profile of theophylline from SCMC- containing capsules (Figs 7-9) was such that, for Batch A (5, 10 and 15%) capsules, Tw,T, values were, 8,13;11,16 and 13,25 minutes respectively. The releasestrend In terms of T, values was Batch C > Batch B > Batch A. To a great extent the dissolution rate of SCMC-contahing capsules decreased as the particle size decreased. However, the work of Prescott et aIt3 on the effect of size differences on the dissolution rate and bioavallabllity of phenacetln is of the reverse order - dissolution rate lncreased with decrease in

Flg 7: K Rslsaesd ve Tlme(mln) for thsophylllns capeult~(batch A) oontalnlng dltlerenl

conoentratlona of SCMC

Flg 8: % ~kleased vs ~l&(rnln) for theophylllne capsules (batch 8) contalnlng dlfferenl cdcenlrallons

of SCMC

44

particle size. This size-dependent dissolution behaviour of SCMC-contdlning theophylline capsules is attributed to the formation of aggregates, which maintained the capsule shape even after the dissolution and ercdm of the capsule shell. This sustained aggregate is presumed to be due to gellation, and depleted in size through erosion as dissolution progressed.

Flg 8: % Released vs Tlme(mln) for lheophylllne capsules(batch C) con(e1nlng different .

concentrations of SCMC

The release profile of theophylline from capsules containing tragacanth (Figs 10-12) showed that for Batch A capsules, there was a decrease in dissolution rate as the concentration of the binder lncreased, as reflected by the T,, values of 13, 18 and 33 minutes at 5, 10 and 15% concentrations respectively. The slowest release was exhibited by Batch B capsules, with T, of 50, 76 and 76 minutes followed by Batch C capsules wtth T, values of 43, 56 and 24minutes .respectively.

The general release characteristics in terms of T,, values amongst the binders was such that for Batch A capsules, tragacanth > Tacca starch > maize starch > SCMC; for Batch B capsules, tragacanth > Tacca starch > maize starch. > SCMC; for Batch C capsules, tragacanth . SCMC > Tacca starch > maize starch. For theophylline, immediate release is still highly recommended for fast bronchospasm relief. Tacca starch was not found to be at any of the release extremes and i t is suitable et any particle size for the release

'

of theophylline in the GfT for asthmatic re!ief. Therefore, manipulation of the particle size of theophylline granules could be a potential means of correcting its bioavailabilityl

West African Journal of Pharmacy (2067) 2qf) >


d bioequivalence problems, except in its sustained release forms. Although particle size reduction remains an acceptable method of increasing dissolution rates, it must not be assumed that smaller particles ar granules will always exhibit faster dissolution beliaviour than coarse or bigger particles or granules. Aggregation sustained by the binding action of mucilage may reduce the effective surface area in contact with the dissolution medium, through viscous gel formation.

5 10 15 20 30 40 50 60 90 120150180 Tlme (mln)

Flg 10: % Released vs Tlme(mln) lor theophylllne capsules (batch A) contalnlng dlfferent

concentratlone of tragacanth

Flg 11: % Releaaed vs Tlme(m1n) lor theophylllne cepsules(batch B) contmlnlng dlfferent

concentretlons of tragacanth

West African Joumal of Pharmacy (2007) 20(1)

Fig 12: % Releaeed ve Tlme(m1n) for theophylllne capsules(batch C) contalnlng different

concentrations of tragacanth

The effect of S.I.F/S.GF The dissolution profile of theophylline from Batch A

capsules containing 15% binder in O.IN HCI, simulated gastric fluid without pepsin (SGF) and simulated intestinal fluid without pancreatin (SIF) are shown in Figs 1,18 and 19. The trend of release exhibited by the gel forming binders differed from the two starches. The release rate trend for capsules containing 15% SCMC or tragacanth was 0.1N HCI > SIF > SGF, while for 15% Tacca starch-containing capsules, it was SIF > SGF =O.lN HCI. For Maize starch- containing capsules, fastest release was in SGF followed by SIF and then 0.1.N HCI. Their T,, values showed no remarkable differences. For Tacca-containing capsules, there was similar dissolution time in both 0.1N HCI and SGF. The indication here is that OJN HCI with or without pepsin may be used in place of simulated gastric fluid for the evaluation of dissolution parameters.

Some workersq4. ' 5 have earlier reported the influence of pH on the release of theophylline from tablets. It has also been shown that the release is more rapid in alkaline medium, this being attributed to the dissolution of the incorporated cellulose acetate phthalate at that pH. Tables 1-3 show the higher T,,T, values for capsules containing Tacca or maize starch in 0.1 N HCI than in SIF. The T,T, for those of Tacca starch however exceeded those of maize starch in SIF and other fluids. Such decreased T, T, values in alkaline pH (SIF) exhibited by capsules containing maize or Tacca starch, agree with the work of McGinity et allB. Theophylline acts both as a weak acid and baseq7. According to the equation Cs = Log Ks + pH, the solubility (Cs) of a

* , *.-! N. C. OBlTTE AND A. CHUKWU

weak acid actually represents the concentration of the drug in the diffusion layer and would increase with an increase in pH1! The pH increase Is further elucidated by the fact that the pH of gelatinized Tacca starch in deionized water is weakly acidic at 6.61. Therefore in the presence OESIF (pH 7.5) solubility is expected to be high hence the recorded increase in dissolution rate in this alkaline medium.

On the other hand, for the tragacanth or SCMC- containing capsules, the release was slower in SIF than in O.1N HCL. A similar observation has also been made by Ubatn, in which release was slower in SIF than in O.1N HCL. This was attributed to the weak alkaline nature of one of the tablet excipients (dicalcium phosphate dihydrate) and subsequent reduction in solubility. The viscosity of SCMC only decreases markedly at pH below 5 (stable viscosity is within pH 5-10) and the maximum viscosity of tragacanth is at pH 8 (stable viscosity is within pH 4-7.5)20n 2t. This would mean that in SIF and at pH 7.5, the capsules maintained adequate gel viscosity, which slowed down theophylline release.

In SGF, theophylline release from capsules containing SCMC or tragacanth was very reduced, release being slower in those containing tragacanth than SCMC. The presence of NaCI, a constituent of SGF, which is known to reduce the solubility of theophylline, may have contributed to the above observation.

The effect of particle size combination on the dissolutlon of Theophylline capsules

The combined particles are Batch E (125mg of 1.7mm 125mg of 0.25mm undersize) or Batch F (1.25mg of 1.7mm 125mg of 1 .Omm) containing 15% binder concentration. For SCMC or tragacanth-containing capsules, theophylline

-u- Batch C

Flg 13: X Rebemod vm Tlme(mWI) Tor lheophylllne capeulea@atchea A.B andC) contnlnlng 1 0 U gum

blend(trsgacanlh + Taccs starch)

4 Batch B

Fig 14: % Released vs Tlme(mln) for theophylline capsules(batches A,B and C) contalnlng 10 X gum

blend(SCMC + Tacca starch)

Flg 15: Released ve Tlme(mln) for thaophylllne ca~sules(batches A,B and C ) contalnlng ioOi gum

blend(melze starch + Tacca starch)

release from Batch F was faster than from Batch E, as shown in Figs 16-17. For capsules containing Tacca or maize starch, the reverse was the case - Batch E released drug faster than Batch F. For tragacanth, Batch F T, was 40 minutes, Batch E, T, was 60 minutes; for SCMC, Batch F, T, was 35 minutes, Batch E, T, was 64 minutes. But for Tacca starch, Batch F, T, was 13 minutes, Batch E, T, was 4 minutes; For maize starch, Batch F, T, was 6 minutes, Batch E, T, was 2 minutes. , . .

West African Journal of Pharmacy (2007) 2ql )

DISSOLUTION OF THEOPHYLLINE CAPSULE6 CONTAININQ TACCA INVOLUCRATA STARCH

5 10 20 30 40 5 0 ! ' 6 0 9 0 120150180210 Tlme(m1n)

t - . I I .., . . . . . , I

Fig 16:. % Releaeed ve4l1he(mln),for theophylllne capsules(batch,E) contalnlng 15% of blnder

I - 8 . t ,

. 6 . t , . I ' . . , . I , I !

Flg 17: X Released vs Time(m1n) for theophylllne capsules(batchF) contalnlng 15% blnder

5 10 20 30 40 50 60 90 120 150 180 Tlme(mln)

Flg 18 : X Released vs Tlme+nln) In SQF lor theophylllne capsules(batch A) contalnlng 15%

blnder

o ! , . , . . . . . c . * 5 10 . 2 0 30 40 50 60 90 120 150 180

Tlme(mln) Flg 18 : % Released vs Tlme(mln) In SGF lor

theophylllne capsules(ba1ch A) contalnlng 15% blnder

The above results for Tacca or maize starch reveal that the blend of equal amount of large and smalllsmaller encapsulated granules enhanced an overall drug release than their uncombined granules as in Batches A, B or C. The T, of 21, 22 and 15min respectively tor Batches A, B and C of 15% Tacca starch capsules decreased to 13min in Batch F and 5min in Batch E capsules. The smaller particles, which were Inter-packed with the Batch A granules seemed to have been easily permea3d by the dissolution medium (0.1N HCI) without viscous gel formation. On the other hand


N. C. OBITTE AND A. CHUKWU

Flg 19: X Released va Tlme(mln) In SIF lor theophylllne capsulss(batch A) conlalnlng 16%

binder ooncentratlon

0 -I 2 4 8 10 12 16 20 40 60

Time (mln)

Flg 20: Released vs Tlme(mln) for theophylllne capsul4e conlalnlng no gum(blnder)

for tragacanth and SCMC-containing capsules, there was recorded slower release compared to the uncombined Batch A or C, e#dDpt for Batch Rcapsules as shown in Table 3. The influen&!.of particle size combination at 15% binder (SCMC or tragacanth) concentration on the release rate of theophylline is attributable to the predictable increase in intracapsular bulk density and decreased percentage void upon infilling of the spaces created by the Batch A granules with the smaller ones from the mix wilhin the capsule. This would slow down water permeation, encourage viscous gel

Tablo 1: Uniformity of Weight and Content Values of Batch A Capsules

Tacca starch 10 252.0 101.6 Tacca starch 15 253.5 104.5

Tragacanth 5 Tragacanth 10 Tragacanth 15

Maize starch 5 253.0 99.6 Maize starch 10 254.5 102.9 Maize starch 15 252.0 106.2

SCMC 5 254.5 97.5 SCMC 10 256.5 100.3 SCMC 15 --- 252.0 ' 100.8 No Binder 253.5 98.8

Table2:The Various T50,T70 Values obtained for Varlous Formulatlons In SGF and SIF

-,

Binder Concentration

Maize Starch 15% Tixca Starch 15% SCMC 15% Tragacanth 15%

IN SGF. Batch A

(min) (mln)

2 7 4 9 60 9 7

IN SIF Batch A

formation and consequently slow down drug release. This phenomenon could be exploited in the formulation of sustained release capsules.

The effect of gum blendson the dlssolutlon of Theophylilne from Its capsules

The dissolution profile of capsules containing 10% of the gum blends at 1 :I ratio (5% Tacca starch + 5% Iragacanth, maize starch or SCMC), i.e. Tacca starch + tragacanth, Tacca starch + SCMC and Tacca starch + maize starch, are shown in Figs 13-15. The dissolution time of theophylline for Batch C was approximately double or more than that for Batch A.

When compared to capsules of unblended 10% Tacca starch, the presence of 5% of either tragacanth, SCMC or maize starch in their blends with 5% Tacca starch did not Increase the T, of theophylline, rather, in most cases and at all particle sizes, the T, of capsules containing unblended 10% Tdcca starch was much higher than the T,, of the blends (except in the case of Batch A of Tacca starch +

Wed African Journal of Pharmacy (2007) 20(1)


Table3: The aridu us T, andT,, Values Obtained from the Slopesof the Graph of % Drug Released Vs Time In 0. I NHCl medlum

Blnder Concentration ',

Maize Starch Tacca Starch SCMC 1 t Tragacanth ;Trag. + Tacca Starch, p,, SCMC 4- Tacca Starch . i : Maize St: + TAcca St. . '

a No. Binder

M. st. T.St. ,I , > ,,% ;, SCMC ' u * - , , r Tragacanth

. .Trag. + Tacca Starch , SCMC + ~ac'ca Starch Maize St + Tacca St No. Binder

Batch A -- ~

Batch B 1 E

Table 4:The Various T50,l70 Values In 0. IN HCI

- 15% -

9 15 3 0 24

T, , Values .. I 1

- 2 5

30 . 50

50 "T,~ Values

Binder Conc. Batch F Batch E

Maize Starch 15% 6 2 Tacca Starch 15% 13 SCMC 15% ' 35 64 Tragacanth 16?& ' 40 " 60 Maize Starch 15% 13 5 Tacca Starch 15%, 28 14 SCMC 15% 65 132

tragacanth which was more by 1 minute). Similarly, when 2. compared to capsules containing unblended 10% tragacanth, SCMC or Maize starch, the presence of Tacca starch in their blends caused no decrease in the release of theophylline from Batch A of all the blends, Batch B or C of 3. Tacca starch + tragacanth and Batch B of Tacca starch + SCMC. These observations are important when fast release of theophyliine is essential. Blending of equal halves of the 4. imported binder and Tacca starch did not indicate significant variations in release rate when compared to the imported expensive binders. The blending of imported or expensive binders with Tacca starch would reduce costs of production.

~ , ~ a ~ u e s

T,, Values

resulted from their capsules. Theophylline release from capsules containing 15% Tacca starch was faster from Batch E (1.7mm + 0.25mm undersize) than from Batch F (1.7mm + 1.Omm). It can therefore be concluded that from the release characteristics of capsules prepared with Tacca starch reported above, thls locally processed raw material can find useful application in drug capsule for,mulations.

I N '

REFERENCES 1. Chukwu A. (2001). Key points in pharrnaceutlcal

formulation and industrial pharmacy, Mike Social press, Nsukka, pp 1-3.

CONCLUSI@. . 5. The release of theophyliine from capsules containing

15% Tacca involucrata starch was faster in SIF than SGF or 0. IN HCI. In most cases when Tacca starch was blended with tragacanth, SCMC or Maize starch, faster drug release

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