tableting functionality evaluation of prosolv easytab in comparison to physical mixtures of its...

499

Tableting functionality evaluation of Prosolv Easytab in comparison to physical mixtures of its individual components

A. Aljaberi1*, A. Ardakani2, A. Khdair1, S.A. Abdel-Rahim1, E. Meqdadi1, M. Ayyash1, G.M. Alobaidi1, N. Al-Zoubi1

1Department of Pharmaceutical Sciences and Pharmaceutics, 2Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmacy, Applied Science University, PO Box 926296, Amman 11931, Jordan

*Correspondence: [email protected]

Prosolv Easytab is a recently introduced all-in-one excipient for direct compression. The aim of this work was to compare the compaction and dissolution functionalities of Prosolv Easytab versus equivalent physical mixtures of microcrystalline cellulose (MCC) or silicified microcrystalline cellulose (Prosolv SMCC) with complementary excipients. Lutrol F68 was used as a free flowing and poorly compactable model material for the comparison of the compaction functionality, and carbamazepine was used as a poorly soluble model drug for the investigation of the dissolution rate and dissolution stability after storage under accelerated stability conditions. Results showed that Prosolv Easytab produced comparable compactibility, dissolution and dissolution stability to its analogous physical mixtures based on MCC or Prosolv SMCC. The current findings suggest that Prosolv Easytab is functionally equivalent to physical mixture of its components, with obvious advantages regarding simplicity of manufacture and the potential masking of undesirable properties of individual components.

Key words: Prosolv Easytab – Prosolv SMCC – Microcrystalline cellulose – Silicified microcrystalline cellulose – Co-processed excipients – Compactibility.

J. DRUG DEL. SCI. TECH., 23 (5) 499-504 2013

Tablet production by direct compression (DC) is highly preferred because of its simplicity, cost effectiveness and avoidance of stability problems associated with the use of solvent and/or high temperature during wet granulation [1]. One of the requirements of the DC process is the use of suitable diluents that are characterized by excellent flow and compaction properties. Originally, physical mixtures of single-component excipients were used for such a purpose. However, a new successful approach relying on the development of co-processed ex-cipients has taken the initiative to further simplify the straightforward DC process [2, 3]. This new class of excipients contains in addition to the diluent other excipients such as binders, glidants, disintegrants, and recently, lubricants. In co-processed excipients, the interaction of the different com-ponents at the subparticle level results in new physically-engineered particles that maintain the advantages of the base excipient combined with functional qualities of the additional components [4]. Moreover, they have been shown to exert superior functionalities as compared to the physical mixture of the individual components. Examples include improved compactibility and tablet strength [5,6], superior anti-adherent ability and dissolution stability [7], increased resistance to lubricant sensitivity [8], enhanced flow properties [9], and decreased disintegration time [10]. In 2010, JRS Pharma introduced the all-in-one excipient Prosolv Easytab [11]. This ready-to-use excipient is made by co-processing microcrystalline cellulose (a dry binder), colloidal silicon dioxide (a glidant), sodium starch glycolate (a disintegrant), and sodium stearyl fumarate (a lubricant) at 96.5:2:1:0.5 ratios. Evidently, its compre-hensive composition would make it ready for DC of conventional tablets by just mixing with the API. In addition, it is claimed to offer superior flowability, better compactibility, excellent formulation and dissolution robustness, improved weight and API content uniformity, and reduced sticking and capping [12]. However, systematic comparison of the behavior of this new excipient with its Prosolv SMCC 90 and microcrystalline cellulose-based physical mixtures has not been attempted. Moreover, informa-tion regarding its stability-related functionalities upon storage are not available. Toward this effort, the current work was carried out to

evaluate the claimed superior functionalities as well as the applicabil-ity of Prosolv Easytab in the DC process and compare that with the aforementioned physical mixtures. Three excipient functionalities, namely, compactibility, dissolution, and dissolution stability were investigated. Potential benefits of Prosolv Easytab are demonstrated and discussed.

I. MATERIALS AND METHODS1. Materials Prosolv Easytab, Prosolv SMCC 90, Sodium stearyl fumarate (Pruv), sodium starch glycolate (Vivastar), and microcrystalline cel-lulose (Emcocel 90M) were kindly supplied by JRS Pharma GmbH & Co. KG (Rosenberg, Germany). Poloxamer 188 (Lutrol F68) and carbamazepine were kindly supplied by BASF SE (Ludwigshafen, Germany). Colloidal silicon dioxide (CAB-O-SIL M-5) was obtained from Cabot GmbH (Hanau, Germany). Sodium lauryl sulfate was from Spectrum (New Brunswick, New Jersey, United States). A review of several physical characteristics of the MCC brands used as well as a physical mixture representing Prosolv Easytab is presented in Table I [12-14].

Table I - Physical characteristics of the direct compression diluents used in this study.

Emcocel 90M

Physical mixture

Prosolv SMCC 90

Prosolv Easytab

Average particle

size (µm)100 - 110 140

Bulk den-sity (g/L) 250-370 346 250-370 300-420

Angle of repose (°) 34.4 34 28 28

Specific surface

area (m2/g)1.3 3.6 5.6 6.4

500

2. Preparation of powder blends for direct compression Compositions of the various powder blends that were prepared for evaluating the compactibility and dissolution functionalities of Prosolv Easytab, Prosolv SMCC 90, and the physical mixture of their individual components are summarized in Table II. The batch size of each final blend was set at 700 g. Colloidal silicon dioxide and so-dium stearyl fumarate were delumped prior to addition by pre-sieving through #25 and #80 mesh sieves, respectively. Blending was carried out at 30 rpm in a cubic blender connected to a multipurpose motor drive (Kraemer Elektronik GmbH, Darmstadt, Germany). Prosolv Easytab-based formulations required no lubrication step as the lubri-cant is already included within this co-processed excipient, ready for direct compression. Therefore, the quantities of Prosolv Easytab and Lutrol F68 or carbamazepine were weighed and mixed for 15 min. On the other hand, for the Prosolv SMCC 90 and physical mixture-based formulations, all of the formulation ingredients except for the lubricant were weighed and mixed for 15 min. Afterwards, sodium stearyl fumarate was added and mixed with the rest of the powder for 5 min to obtain the final blends. 3. Tableting and compaction studies The various final blends were compressed on an instrumented Erweka EP-1 single punch eccentric tablet press (Erweka GmbH, Heusenstamm, Germany). Tablets of a total weight of 350 mg were prepared (Table II) with a 10 mm standard concave round tooling. Compression force to construct the compaction profiles was obtained using a DPM-3 load cell meter installed on the Erweka EP-1 tablet press (Transducer Techniques Inc., Temecula, CA, United States). At each compression force used, the breaking forces of 10 tablets were tested using an Erweka TBH 325 hardness tester (Erweka GmbH, Heusenstamm, Germany) and the average was used to construct the corresponding compaction profile. Tableting of the various final blends containing the model drug carbamazepine was continued at the target compression force (corresponding to a tablet breaking force of ~ 225 N) to make tablets for testing the dissolution functionality of the different powder blends.

4. Accelerated stability study Three random samples (25 tablets each) of the carbamazepine 100 mg tablets prepared from various formulations described in Table II

were placed in open, wide mouth HDPE bottles. In parallel, another three similar samples were placed in tightly sealed bottles. All bottles were stored for 1 month in a humidity test cabinet pre-equilibrated to 40 °C/75 % RH (Sheldon Manufacturing, Inc., Cornelius, OR, United States).

5. Disintegration time and moisture content determination Disintegration time was measured by placing 6 tablets of each formulation separately in a QC-21 tablet disintegration tester (Hanson Research, Chatsworth, CA, United States) in 900 mL deionized water maintained at 37 ± 2 °C. The moisture content of the tablets denoted as a loss on drying percentage was determined using an infrared mois-ture balance (A&D Co. Ltd., Tokyo, Japan). Briefly, four tablets were crushed by a mortar and pestle and the fine powder was subjected to heat at 90 °C for 2 min.

6. Dissolution testing A Pharmatest dissolution system (Model PTW II; Hamburg, Germany) with a USP apparatus 2 was used for dissolution studies of freshly prepared tablets as well as tablets stored in open and sealed conditions at 40 °C/75 % RH. The dissolution medium was 900 mL of 1 % SLS in deionized water at 37 °C, and the paddle rotating speed was 75 rpm. Filtered aliquots of a 10 mL volume were sampled at predeter-mined time intervals for 90 min. The withdrawn samples were diluted with 1 % SLS solution and then analyzed spectrophotometrically at a wavelength of 288 nm using a Spectronic 601 UV spectrophotometer (Milton Roy, Ivyland, PA, United States). All the measurements were performed in triplicate and the amount of carbamazepine released was determined using a respective calibration curve.

II. RESULTS1. Compaction functionality Initially, compaction profiles of placebo formulations of the three MCC-based excipients were constructed to evaluate the behavior of these excipients in the absence of drugs. As Figure 1A shows, all three formulations were highly compressible. Nevertheless, the Pro-solv Easytab-based formulation (PE-0) which contains the lubricant being co-processed with the rest of the ingredients resulted in lower compaction than the Prosolv SMCC 90 (PS-0) or the physical mixture-based formulation (PM-0). However, it is of the utmost significance to

Table II - Composition of various formulations prepared for direct compression.PM-0 PM-10 PM-20 PM-30 PM-40 PM-50 PM-CBZ

Physical mixture-based formulationsEmcocel 90MCAB-O-SIL

VivastarPruv

Lutrol F68Carbamazepine

Total

337.757

3.51.75

--

350

303.9756.3

3.151.575

35-

350

270.25.62.81.470-

350

236.4254.9

2.451.225105

-350

202.654.22.1

1.05140

-350

168.8753.5

1.750.875175

-350

241.255

2.51.25

-100350

Prosolv SMCC-based formulationsProsolv SMCC

VivastarPruv


Total

344.753.5

1.75--

350

310.2753.15

1.57535-

350

275.82.81.470-

350

241.3252.45

1.225105

-350

206.852.1

1.05140

-350

172.3751.75

0.875175

-350

246.252.5

1.25-

100350

Prosolv Easytab-based formulationsProsolv Easytab


Total

350--

350

31535-

350

28070-

350

245105

-350

210140

-350

175175

-350

250-

100350

Tableting functionality evaluation of Prosolv Easytab in comparisonto physical mixtures of its individual components

A. Aljaberi, A. Ardakani, A. Khdair, S.A. Abdel-Rahim, E. Meqdadi, M. Ayyash, G.M. Alobaidi, N. Al-Zoubi


501

evaluate the compaction functionality of these excipients in real life situation; i.e., in the presence of varying levels of poorly compress-ible drugs. Unfortunately, preliminary attempts to incorporate poorly compressible drugs compromised the flowability and, subsequently, the tabletability of the formulation. This restricted the amount of the poorly compressible drug that can be included and, thus, no meaning-ful insight on the compaction functionality of the excipients under investigation could be obtained. To overcome this obstacle, Lutrol F68 was included instead. Lutrol F68 is a highly flowable, prilled material with an average particle size of 1000 μm [15]. Its poor compressibility and high stickiness potential make it an excellent model substance for the current purpose. The compaction profiles of various formulations of the three MCC-based excipients containing Lutrol F68 at varying levels from 10 to 50 % are presented in Figure 1B-F. At a level as low as 10 % Lutrol F68, the compaction properties of the Prosolv Easytab-based formulation, PE-10, was similar to those of the physical mixture-based formulation, PM-10, at all compression forces. On the other hand, the Prosolv SMCC-based formulation, PS-10, showed similar compactibility to the other two formulations at low compression forces. At higher compression forces, however, Prosolv SMCC appears to be more compactible than the Prosolv Easytab or the physical mixture (Figure 1B). The superior compactibility of Prosolv SMCC-based formulation could be seen clearly up to 20 % level of the poorly compressible Lutrol F68 (Figure 1C). Inclusion of a higher level of Lutrol F68 resulted in similar compaction profiles of all three formulations (Figure 1D-F). Likewise, Figure 2 shows that similar compactibility was seen for all three formulations containing the model drug carbamazepine at a level of 28.5 %. 2. Physical stability Tablets of various formulations containing 100 mg carbamazepine were prepared as discussed earlier at a tablet breaking force of ~ 225 N (Table III). After one month storage in sealed bottles at 40 °C/75 % RH conditions, the tablet breaking force was slightly decreased for all three formulations. The difference between breaking force values before and after storage under the aforementioned conditions was 10, 24.5, and 40.1 N for the PE-CBZ, PM-CBZ, and PS-CBZ, respec-tively. When tablets from the same formulations were stored at these stress conditions in open bottles, the Prosolv SMCC- and the Prosolv Easytab-based formulations preserved their tablet breaking force better than the physical mixture-based formulation. The difference between breaking force values before and after storage in this case were 73.4, 82.2, and 100.6 N for the PS-CBZ, PE-CBZ, and PM-CBZ, respectively. Therefore, taking the difference between breaking force values before and after storage as an indicator of breaking force and compaction stability shows that the Prosolv SMCC- and the Prosolv

Tabl

et b

reak

ing

forc

e (N

)

0

100

200

300

400

500

PM-0PS-0PE-0

Tabl

et b

reak

ing

forc

e (N

)

Compression force (KN)

Tabl

et b

reak

ing

forc

e (N

)


0 5 10 15 20 250

100

200

300

400

500

0 5 10 15 20 25

0

100

200

300

400

500

0 5 10 15 20 250

100

200

300

400

500

0 5 10 15 20 25

0

100

200

300

400

500

0 5 10 15 20 250

100

200

300

400

500

0 5 10 15 20 25

A B

D D

E F

PM-10PS-10PE-10

PM-20PS-20PE-20

PM-30PS-30PE-30

PM-40PS-40PE-40

PM-50PS-50PE-50

Figure 1 - Compactibility profiles of physical mixture-based formulations (PM), Prosolv SMCC-based formulations (PS), and Prosolv Easytab-based formulations (PE) containing from 0 to 50 % of Lutrol F68.

Table III - Characteristics of tablets from various carbamazepine-containing formulations when (A) freshly prepared, (B) stored for three days at room temperature in sealed bottles, (C) stored for one month at 40 °C/75 % RH conditions in open bottles, and (D) stored for one month at 40 °C/75 % RH conditions in sealed bottles.

Breaking force (N) Moisture content (%) Thickness (mm) Diameter (mm) Disintegration time (s)A PM-CBZ

PS-CBZPE-CBZ

228.0 ± 17.1228.2 ± 13.5223.0 ± 16.4

32.83.3

4.11 ± 0.04 4.04 ± 0.054.10 ± 0.06

10.04 ± 0.0210.03 ± 0.0210.03 ± 0.01

292523

B PM-CBZPS-CBZPE-CBZ

230.3 ± 10.2231.7 ± 7.7223.5 ± 9.5

32.93.3

4.07 ± 0.034.05 ± 0.024.08 ± 0.02

10.02 ± 0.0210.01 ± 0.0110.04 ± 0.01

242025

C PM-CBZPS-CBZPE-CBZ

127.4 ± 7.2154.8 ± 3.4140.8 ± 6.1

2.92.92.8

4.29 ± 0.034.24 ± 0.044.30 ± 0.02

10.10 ± 0.0110.14 ± 0.0110.10 ± 0.01

202220

D PM-CBZPS-CBZPE-CBZ

203.5 ± 11.5187.8 ± 13.0213.0 ± 8.4

2.82.22.2

4.16 ± 0.034.14 ± 0.084.16 ± 0.04

10.07 ± 0.0110.05 ± 0.0210.06 ± 0.02

351920


Tabl

et b

reak

ing

forc

e (N

)

0

100

200

300

400

500

PM-CBZPS-CBZPE-CBZ

0 5 10 15 20 25

Figure 2 - Compactibility profiles of physical mixture-based formulation (PM), Prosolv SMCC-based formulation (PS), and Prosolv Easytab-based formulation (PE) containing 28.5 % of carbamazepine.

Tableting functionality evaluation of Prosolv Easytab in comparisonto physical mixtures of its individual componentsA. Aljaberi, A. Ardakani, A. Khdair, S.A. Abdel-Rahim, E. Meqdadi, M. Ayyash, G.M. Alobaidi, N. Al-Zoubi


502

Easytab-based formulations offer similar functionality, which is slightly superior than physical mixture-based formulation. Viscoelastic expansion (relaxation) of the manufactured tablets upon storage at various conditions was assessed by monitoring tablet diameter and thickness. As Table III shows, no expansion took place over three days of storage of tablets from all three formulations placed in sealed bottles at room temperature. However, a significant increase in tablet dimensions resulted after exposure to 40 °C/75 % RH condi-tions for one month. The increase in tablet thickness and diameter was considerably higher when the tablets were placed in open bottles and exposed to these stress conditions. Interestingly, this increase was not accompanied by an increase of the moisture content of the tablets. On the contrary, storage in sealed bottles for one month at 40 °C/75 % RH conditions dried the PS-CBZ and PE-CBZ tablets. The moisture content of these tablets was lower than that of the freshly prepared tablets. On the other hand, the moisture content of the PM-CBZ tablets after storage at various conditions remained comparable to the freshly prepared tablets.

3. Dissolution stability The dissolution profiles of carbamazepine tablets prepared from all three formulations determined immediately after compression are presented in Figure 3. The freshly prepared tablets from the three formulations resulted in comparatively similar dissolution rates of the model drug. However, when tablets from various formulations were stored for a period of one month in open bottles at 40 °C/75 % RH conditions, a significant decrease in the dissolution rate could be observed irrespective of the MCC brand used (Figures 4, 5 and 6). Nevertheless, the decrease in the dissolution rate was not the same with the three MCC brands used. To further illustrate this effect, the absolute difference in the percentage released between initial and exposed samples was plotted as a function of time (Figure 7A). The order of the three MCC brands with regard to dissolution stability was Prosolv SMCC > Prosolv Easytab > MCC, with Prosolv SMCC resulting in the most dissolution-stable tablets. The disintegration times of these tablets before and after storage are summarized in Table III. Apparently, the differences observed in the dissolution rates are not related to disintegration issues as all the formulation required only 19 to 35 s to disintegrate completely. The decrease in dissolution rate appears to be more influenced by the exposure to high relative humidity rather than being an elevated-temperature effect. Improved dissolution stability was observed when tablets from various formulations were placed in sealed bottles instead and exposed to stress conditions for one month. Under these condi-tions, similar dissolution profiles of PM-CBZ and PS-CBZ tablets were observed (Figures 4 and 5). On the other hand, a slightly slower dissolution rate was seen at early time points for the Prosolv Easytab-based formulation PE-CBZ (Figure 6). Nevertheless, the percentages of the dissolved carbamazepine from the fresh and stressed tablets were almost identical at the time point of 25 min and greater for this formu-lation. Considering the absolute difference in the percentage released between initial and stressed samples in sealed bottles presented in Figure 7B, the dissolution stability of the three MCC derivatives could not be ordered in a meaningful way. On one hand, the Prosolv Easytab formulation appears to be the least dissolution stable formulation up to 25 min of dissolution; then, it shows the maximum stability from that time point forward. Conversely, the exact opposite is observed for the physical mixture-based formulation.

III. DISCUSSION The work presented herein is primarily focused on comparing the excipient functionality of the recently introduced Prosolv Easytab with its predecessor Prosolv SMCC and the physical mixture represent-ing this new excipient. Three types of formulations were prepared and investigated: i) physical mixture-based formulation, ii) Prosolv

Time (min)

% d

isso

lved

0

20

40

60

80

100

PM-CBZPS-CBZPE-CBZ

0 15 30 45 60 75 90

Figure 3 - Dissolution profiles of freshly prepared carbamazepine tablets from physical mixture-based formulation (PM), Prosolv SMCC-based formulation (PS), and Prosolv Easytab-based formulation.

FreshSealed bottleOpen bottle

Time (min)

% d

isso

lved

0

20

40

60

80

100

0 15 30 45 60 75 90

Figure 4 - Dissolution profiles of carbamazepine tablets prepared with the physical mixture-based formulation, initially and after one month exposure to 40 °C/75 % RH in open or sealed bottles.


Time (min)

% d

isso

lved

0

20

40

60

80

100

0 15 30 45 60 75 90

Figure 5 - Dissolution profiles of carbamazepine tablets prepared with the Prosolv SMCC-based formulation, initially and after one month exposure to 40 °C/75 % RH in open or sealed bottles.


Time (min)

% d

isso

lved

0

20

40

60

80

100

0 15 30 45 60 75 90

Figure 6 - Dissolution profiles of carbamazepine tablets prepared with the Prosolv Easytab-based formulation, initially and after one month exposure to 40 °C/75 % RH in open or sealed bottles.




503

SMCC-based formulations, and iii) Prosolv Easytab-based formula-tions. As shown in Table II, they were referred to as PM, PS and PE formulations, respectively. The first excipient functionality of these formulations investigated was their compactibility as a direct compression diluent. As mentioned earlier, poorly compressible drugs are often poorly flowable as well, resulting in tabletability issues when intended to be incorporated at satisfactory levels. Therefore, several poorly compressible materials were screened and the decision was taken to use Lutrol F68 as a model poorly compressible and sticky substance to challenge the various formulations. Remarkably, all three formulations could incorporate as high as 50 % of Lutrol F68 before any signs of stickiness started to appear. Moreover, acceptable tablet breaking force values of 120-140 N could be obtained at this Lutrol F68 level (Figure 1). It is worth noting that all three formulations were equivalent from a compaction point of view at levels of Lutrol F68 equal to 30 % or higher. Below that level, the Prosolv SMCC-based formulations showed moderately better compaction than the Prosolv Easytab- or the physical mixture-based formulations. Nevertheless, this apparently superior compactibility of Prosolv SMCC-based formulation is of no practical advantage as it is only seen at compression forces corresponding to tablet breaking force values > 250 N. Such very high tablet breaking force is expected to impair the disintegration and dissolution of the relatively small tablets prepared in this study. Moreover, tablets exhibiting very high breaking force or other related quality attributes can be easily obtained with the Prosolv Easytab or the physical mixture-based formulations by simply using higher compression forces. Tablets from the various formulations containing 28.5 % of the model drug carbamazepine were compressed. These tablets were found to soften and swell when aged for one month under increased temperature and humidity conditions. Reduction in the tablet breaking force correlates with the viscoelastic expansion of the compressed diluent (Table III). This viscoelastic expansion was observed when the tablets were stored in open as well as sealed bottles. However,

the expansion in tablet size was not a result of increased moisture sorption. The moisture contents of the tablets stored in open bottles at 40 °C/75 % RH were comparable to freshly prepared tablets. Moreo-ver, lower moisture contents of PE-CBZ and PS-CBZ were observed when storage took place in sealed bottles. This drying effect further confirms that moisture sorption is not the reason for the increased size and softening of the tablets. Nevertheless, the expansion of tablet size appears to be depend-ant on exposure to elevated relative humidity. A larger increase in tablet thickness and diameter and, consequently, greater softening was obtained when tablets were stored in open bottles at 40 °C/75 % RH conditions. The current results suggest that direct exposure to elevated humidity maintained the moisture content of the tablets and caused a higher extent of tablet expansion and softening as compared to storage in sealed bottles. In either case, the extent of softening was comparable for all of the three formulations evaluated. The other investigated excipient functionalities were dissolution and stability on storage. Carbamazepine is a poorly water-soluble amine drug. It has been found that amine drugs have a tendency to be adsorbed onto microcrystalline cellulose and its derivatives [7, 16]. This phenomenon results in a decrease of the dissolution rate of the drug as a function of storage. Therefore, it is of greatest importance to minimize this detrimental effect in order to ensure reproducible product performance. When tablets were placed in open bottles and exposed to stress conditions, the co-processed excipients offered more dissolution stabil-ity than MCC in a physical mixture with colloidal silicon dioxide and other components (Figure 7A). The improved dissolution stability of the co-processed excipients can be attributed to the reduced adsorption of carbamazepine onto the MCC core of these excipients as compared to MCC in the physical mixture. Steele and coworkers showed that the silicification process of MCC reduced the adsorption of a model amine drug onto MCC by 12-21 %. The reduced adsorption is directly related to the replacement of cellulosic area by the nonadsorbing silicon dioxide or the preferential adsorption of silicon dioxide onto the active sites in the surface of MCC [16]. The adsorbing cellulosic surface of Prosolv Easytab is covered additionally by sodium starch glycolate and sodium stearyl fumarate. Consequently, higher carbamazepine release was obtained from tablets formulated with the co-processed excipients as compared to those containing the physical mixture after one-month of storage in open bottles at 40 °C/75 % RH condi-tions. This is in agreement with previous findings comparing MCC, SMCC, or the physical mixture of MCC and colloidal silicon dioxide as extragranular compression aids [7]. On the other hand, storage at stress conditions with protection against elevated humidity by placing the tablets in sealed bottles improved the dissolution stability of the three carbamazepine formulations. In addition, all three formulations showed comparable dissolution stability (Figure 7B). In conclusion, the aforementioned findings show that Prosolv Easytab as a direct compression aid is equivalent from a compaction and dissolution perspective to analogous physical mixtures based on MCC or SMCC with complementary excipients. This equivalency is in no doubt an advantage of Prosolv Easytab over the abovementioned physical mixture counterparts. Using Prosolv Easytab reduces the number of steps during production of tablets into mixing, compres-sion, and coating. No delumping or sieving of formulation ingredients would be required. Furthermore, the lubricant is already co-processed with the rest of the Prosolv Easytab components. Therefore, only one phase of mixing is required to prepare final blends of the drug for compression. The MCC- or SMCC-based physical mixtures will always require a second mixing phase to lubricate the final blends. In addition, issues related to the number of ingredients and varying particle size of the ingredients are expected to be significantly subsided with Prosolv Easytab. These include segregation, mixture homogeneity, and the quality of the tablet in terms of content uniformity. In summary,

Time (min)

% re

leas

e di

�ere

nce

0

5

10

15

20

% re

leas

e di

�ere

nce

0

5

10

15

20

25

A

B

0 15 30 45 60 75 90

Figure 7 - The difference in the percentage of released carbamazepine from various formulations, tested at time zero and after one month exposure to 40 °C/75 % RH in (A) open bottles and (B) sealed bottles. (s) Physical mixture-based formulation, (n) Prosolv SMCC-based formulation, and (l) Prosolv Easytab-based formulation.

Tableting functionality evaluation of Prosolv Easytab in comparisonto physical mixtures of its individual componentsA. Aljaberi, A. Ardakani, A. Khdair, S.A. Abdel-Rahim, E. Meqdadi, M. Ayyash, G.M. Alobaidi, N. Al-Zoubi


504

Prosolv Easytab is a mutli-functional co-processed excipient that produces similar functionalities to physical mixture from its individual components, while improving process-related quality attributes and minimizing undesirable properties that may be associated with the physical mixture.

REFERENCES

1. Armstrong N.A. - Tablet manufacture by direct compression. - In: Swarbrick J. (Ed.), Encyclopedia of Pharmaceutical Technology, New York, Informa Health Care USA, 2007, p. 3673-3683.

2. Bolhuis G.K., Armstrong N.A. - Excipients for direct compaction-an update. - Pharm. Dev. Technol., 11, 111-124, 2009.

3. Gohel M.C., Jogani P.D. - A review of co-processed directly compressible excipients. - J. Pharm. Pharm. Sci., 16, 76-93, 2005.

4. Nachaegari S.K., Bansal A.K. - Coprocessed excipients for solid dosage form. - Pharm. Technol., 28, 52-65, 2004.

5. Arida A.I., Altabakha M.M. - Cellactose a co-processed excipi-ent: a comparison study. - Pharm. Dev. Technol., 13, 165-175, 2008.

6. Muzikova J., Novakova P. - A study of the properties of com-pacts from silicified microcrystalline celluloses. - Drug Dev. Ind. Pharm., 33, 775-781, 2007.

7. Aljaberi A., Chatterji A., Shah N.H., Sandhu H.K. - Functional performance of silicified microcrystalline cellulose versus mi-crocrystalline cellulose: a case study. - Drug Dev. Ind. Pharm., 35, 1066-1071, 2009.

8. Rashid I., Al-Remawi M., Leharne S.A., Chowdhry B.Z., Badwan A. - A novel multifunctional pharmaceutical excipient: modifica-tion of the permeability of starch by processing with magnesium silicate. - Int. J. Pharm., 411, 18-26, 2011.

9. Wagner K.G., Dressler J.A. - A corn starch/alpha-lactose monohydrate compounds as a directly compressible excipi-ent. - Pharm. Technol. Europe, 15, 33-38, 2003.

10. Muzikova J., Eimerova I. - A study of the compaction process and the properties of tablets made of a new co-processed starch excipient. - Drug Dev. Ind. Pharm., 37, 576-582, 2011.

11. Vollmer R., Stoyanov E. - An all-round excipient for direct compression. - Pharm. Technol. Europe, 22, 34, 2010.

12. JRS Pharma LP, Prosolv Easytab: Technical literature. 13. Rowe R.C., Sheskey P.J.,Quinn M.E. - Handbook of Pharma-

ceutical Excipients. - 6th ed., 2009. 14. Lahdenpaa E., Antikainen O., Yliruusi j. - Direct compression

with silicified and non-silicified microcrystalline cellulose : study of some properties of powders and tablets. - STP Pharma Sci., 11, 129-135, 2001

15. BASF SE, Lutrol L and F grades, Technical literature. 16. Steele D.F., Edge S., Tobyn M.J., Moreton R.C., Staniforth J.N.

- Adsorption of an amine drug onto microcrystalline cellulose and silicified microcrystalline cellulose samples. - Drug Dev. Ind. Pharm., 29, 475-487, 2003.

MANUSCRIPT

Received 24 September 2012, accepted for publication 15 January 2013.




tableting functionality evaluation of prosolv easytab in comparison to physical mixtures of its...

Documents