Hydrophilic matrices are developing as an alluring industrial option for development of extended release tablet formulation, as a result of their compatibility with large amount of drugs, variety of types and viscosity grades available and flexibility in dosage form fabrication. But the tremendous cost associated with the synthesis along with safety testing, contour a huge hurdle in the development of novel polymeric materials.
Employing combinations of the pharmaceutically approved polymers serve as a potential way to enhancing polymer performance from matrix formulations and accomplishing desired drug release profiles. Based on this approach, diverse strategies such as Geomatrix technology (Conte and Maggi, 1995), inter-polymer complexes (Park et al., 2007), use of graft copolymers (Ferrero et al., 1996), pulsatile release multilayer tablets (Karavas et al., 2006) etc. have been reported earlier. Most of these approaches use cellulose ethers like HPMC for the purpose of drug release modulation, as the reliable alternative hydrophilic polymers available, are limited.
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The present study proposes three new cost effective, elegant and simple approaches to modulate drug release from hydrophilic extended release matrices by exploiting a new combination of polymers. This approach mainly aims at achieving bimodal drug release pattern, to suit the variations in absorption rate from various sites in GI tract in contrast to typical zero order or time dependent kinetics observed in case of commonly used polymers like HPMC.
The first approach will utilize a new combination of polymers composed of a blend of polyethylene oxide (PEO) and carrageenans (lambda, iota and kappa).The literature survey, demonstrates that, the proposed combination of polymers has not been used earlier. The effect of this blend on the drug release pattern will be examined by preparing a matrix tablet (Tablet I) using varying amounts of these polymers taking ibuprofen as a model drug. With the aim to achieve bimodal drug release pattern, two and three layer systems (Tablet II and III) which will embody the above prepared matrix tablet (Tablet I) as a core and the polymer blend as barrier, is designed in second approach. The third approach intends to prepare a formulation (Tablet IV) by incorporating polyvinyl pyrrolidone (PVP), in the core tablet made up of PEO and carrageenans (Tablet I). The effect of PVP on the modulation of drug release from the core tablet at certain time point (modulation point), will be observed.
To investigate the drug release pattern and characterise the release mechanism from the designed formulations (I to IV), dissolution studies will be carried out using dissolution apparatus and HPLC. The data obtained will be analysed using regression analysis and exponential equation.
The physical characteristics of the prepared tablets will be studied adopting various techniques like friability test, hardness test, viscosity measurements. Also, the nature of the prepared blend will be characterised by determining the viscosity using Brookfield viscometer. The modifications in surface topography, swelling and erosion mechanisms will be studied using advanced techniques like cryogenic scanning electron microscopy and Fourier transformation near infrared spectroscopy.
Thus, by blending different hydrophilic polymers with appropriate viscosity and disintegration rate like PEO and carrageenans and designing a suitable formulation, the overall drug release rate from an extended release system will be modulated.
1.1 General context
Modulation of drug release from a dosage form is a great challenge for many diseases where ideal dosage regimen is required. Pattern of drug release from any dosage form needs to be modulated in such a way that, the desired therapeutic concentration of drug at site of action is attained immediately and then is maintained constant throughout the duration of treatment (Aulton, 2007). In order to maintain steady state plasma concentration, basically zero order release is desired, however occasionally bimodal release may also be required to accommodate the variation in absorption pattern from GI tract (Hardy et al 2006). In the context of this discussion 'modulation of drug release' is assumed to be in such a way that it maintains ideal release pattern and dosage regimen.
Formulations with modulated drug release have many potential advantages like achievement of steady state, decrease in dosing frequency, better patient compliance, reduced toxicity etc. over the conventional dosage form. Many approaches have been developed to modulate drug release. The main approaches include dispersing a drug either in soluble (hydrophilic) matrices or insoluble (hydrophobic) monolithic/matrix system. Out of these the hydrophilic matrix systems are widely employed due to their high efficacy to modulate release as compared to hydrophobic ones (Aulton, 2007). Oral Drug delivery is the preferred route of administration for these systems (Conti et al., 2006). These hydrophilic matrices are basically divided into two types:
Always on Time
Marked to Standard
These systems on interaction with water develop into a cross linked polymeric structure, formed by hydrogen bonds between adjacent polymeric chains. This structure entraps continuous phase in their interstices (Aulton, 2007).
Example: Alginic acid and gelatin.
Figure 1: Representation of true gel matrix
These systems on contact with water, result in entanglement of adjacent polymeric chains with no or minute crosslinking. This entanglement results in formation of very viscous solutions (Aulton, 2007).
Example: HPMC and sodium alginate.
Figure 2: Representation of viscolized matrix
The basic mechanism involved in this system is that, the hydrophilic polymer on contact with GI fluid swells due to conversion of its glassy state to rubbery state and acts as a barrier for the drug release. If the drug is soluble then the release occurs by diffusion whereas in case of insoluble drugs release occurs by erosion followed by dissolution. Following this, a new surface becomes available for absorption of water and forms a gel barrier.
Figure 3: Fronts involved in matrix swelling process
(Silveira et al., 2011, adapted)
The mechanisms which may be involved in proper release of drug through hydrophilic polymeric matrices include:
Case I mechanism or Fickian release which is the most commonly encountered mechanism, where drug release occurs by diffusion through outer gel layer.
Non - Fickian or anomalous transport
Case II mechanism or zero order release (Conti et al 2006).
Amongst the available hydrophilic matrices a very few are able to modulate the release pattern of the drug so as to give a zero-order or bimodal release which is highly desired. It includes cellulose ethers, which have been extensively reviewed in pharmaceutical literature and have gained popularity.But the alternative options available are very few. Due to extensive use of hydrophilic matrices in extended release formulations and developing need for potential polymers to achieve desired release profile, huge amount of screening of synthetic as well as natural polymers is carried out by pharmaceutical industry. But the cost involved in synthesis of new polymers and also the regulatory issues regarding their safety and testing has developed as a great hurdle in development of hydrophilic matrices (Conti et al 2006).
To tackle this problem and to obtain desired release pattern, many approaches have been developed. Out of these approaches "use of combination of polymers" is an upcoming approach of great significance.Although many studies have been carried on use of polymer blends, obtaining technologically acceptable formulation whose release profile is unaffected by other variables like excipients and in-vivo environmental conditions is still a great challenge.
SCIENTIFIC STUDIES ON USE OF POLYMERIC COMBINATIONS
2.1 PREVIOUS INVESTIGATIONS
The need for use of polymer blends in development of extended release formulations has come about by the conversion of many factors like prohibitive cost of synthesizing new polymers, expiration of existing patents, safety and toxicity issues related with the newly synthesized polymers and the improper drug release profiles obtained from existing ones (Conti, 2006).The approach of using potential polymeric blends to develop extended release formulation with desired release profiles emerged around 1990's (Ferrero, 1997). Some of the attractive and successful approaches developed in last two decades include:
2.1.1 Modulation of drug release using Geomatrix multi-layer matrix systems
One aspect of using polymer blends for extended release involves a new multilayer tablet design called Geomatrix, which has been proposed by JagoPharma in 1995 for constant drug release.
In this approach, the hydrophilic matrix was coated with drug free barrier layer either on one or both the bases. These coatings reduce the area of hydrophilic core coming in contact with GI fluid and thus modulate drug release from Geomatrix tablets, resulting in linear extended release profile. This system wasmainly intended for soluble drugs, whereas if employed for insoluble drugs the release may be greatly reduced. Depending upon the type of barrier used in this approach, it was classified into two types:
Gellable/swellable barrier system (G): High viscosity methocel K 100 M was used for this purpose.
Erodible barrier system (E): Low viscosity methocel E 5 was used as erodible barrier.
Figure 4: Multi-layer matrix tablets consisting of two and three layer system (Geomatrix technology)
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(Conte and Maggi, 1995, adapted)
Highly soluble drug like Trapidil and low solubilty drugs like Ketoprofen and Nicardipine hydrochloride were used to study the release profile of Geomatrix system. Gellable barrier on coming in contact with water swells and forms gel layer which is not eroded, thus acting as a barrier for drug release. Whereas the erodible barrier is eroded progressively, resulting in a time dependent exposure of the core for interaction with the GI fluid. The release profile of different drugs was studied using dissolution test apparatus 1 (basket). Swelling and erosion patterns of these systems were observed using penetrometer TA-XT2 texture analyser and video microscope.
Gellable barrier system was found to have high efficiency in modulating the release pattern of soluble drugs, whereas the erodible barrier system was found to be suitable for the sparingly soluble drugs (Conte and Maggi, 1995).
2.1.2 Application of HPMC - Pectin binary polymer in drug release rate modulation
Kim and Fassihi in 1996developed a binary polymer matrix tablet using a blend of pectin and hydroxypropylmethylcellulose (HPMC). In this approach, various ratios of the major components of the formulation (HPMC and pectin) were used and prednisolone was used as drug model. This tablet formulation was developed by direct compression technology and was designed to deliver drug according to zero order release kinetics. Varying ratios of HPMC and pectin in the formulation results in a wide range of viscosities which in turn regulate the drug release from the formulation. Combination of HPMC and pectin contributes to the formation of swelling/erosion boundaries and thus leading to constant drug release from the tablet.
Figure 5: Microscopical changes associated with binary polymer system
(Kim and Fassihi, 1996, adapted)
Hydration and gelation pattern was observed using photo micrographic pictures and found to occur in both axial and radial direction. The power law expression was employed to characterise the release mechanism, analyse the fraction of drug release and release kinetics.
Mt/Mâˆž = ktn
Where,k is kinetic constant and
n is exponent indicative of release mechanism
Pectin: HPMC ratios of 4:5, 3:6, and 2:7 were observed to have nvalues above0.95 which indicates a Case II transport mechanism.
The results of this experiment indicate that zero order release kinetics can be maintained throughout the experiment by increasing pectin: HPMC ratio (Kim and Fassihi, 1996).
2.1.3 Development of hydrophilic matrix tablets using newly synthesized family of graft copolymers of methyl acrylate
A group of hydrophilic matrices called as graft copolymers was newly synthesized by graft copolymerization of methyl methacrylate (MMA). It includes hydroxypropyl starch-methyl methacrylate (HS-MMA), carboxymethyl starch-MMA (CS-MMA), hydroxylpropyl cellulose-MMA (HC-MMA).
The flow properties of these polymers were extensively studied. Theophylline was used as model drug. Polymer and theophylline along with other excipients like stearic acid, anhydrous dicalcium phosphate dehydrate were compressed by direct compression method and a hydrophilic matrix tablet was produced. Dissolution efficiency and swelling capacity of the tablets consisting of different formulations were tested over a period of 8 h. The results obtained are summarised in table below.
Table 1: Dissolution efficiency and swelling capacity of matrix tablets over a period of 8h at different pH
(Ferrero et al, 1997, adapted)
HS-MMAL and NaCMC formulations were found to show satisfactory results with release from NaCMC formulations slightly slower than that of HS-MMAL.
Many other approaches were developed earlier with an intention to achieve zero order or bimodal release. However many of these systems are complex as compared to the simple hydrophilic matrix systems (Ferrero et al, 1997).
2.2 RECENT DEVELOPMENTS
With advancement of knowledge in this area, a number of approaches have been developed recently to modulate drug release using different combination of polymers. Some of these approaches have been developed by improvising or modifying the previous combination of polymers whereas many new approaches have also been developed.
2.2.1 Approaches based on the earlier used combination of polymers
220.127.116.11 Development of pulsatile release formulation with mucoadhesive properties using PVP/HPMC blends.
This study carried out by Karavaset al.in 2006by employing PVP/HPMCis similar to the research on development Geomatrix tablets carried out in 1995. In this work a bi-layered pulsatile release formulation comprising of a felodipine/PVP core coated with a blend of PVP/HPMC was developed.
Figure 6: Design of FELO/PVP 10/90 w/w press coated system
(Karavas et al., 2006, adapted)
The miscibility of this system which is responsible for mucoadhesive properties was studied using DSC. In this system the coating layer on exposure to medium disintegrate first resulting in immediate release of felodipine followed by delayed release due to the PVP/HPMC blend. This system can be employed in pulsatile chronotherapeutics by varying the PVP/HPMC blend ratio and thus modifying its release.
18.104.22.168 Study of modulation of drug release from HPMC based tablets by PVP
Hardy et al. in 2007studied the effect of PVP on release kinetics from HPMC based tablets. It was observed that PVP incorporated in formulation in critical concentration causes reduction in HPMC viscosity leading to zero order or bimodal release kinetics, in contrast to first order kinetics exhibited by HPMC alone. Near infrared microscopy (NIR) was used to study the release from this system.
This effect of PVP on modulation point of HPMC may be the reason for achieving desired kinetics in Geomatrix (Conte and Maggi, 1995) and pulsatile release systems (Karavas et al., 2006)
22.214.171.124 Biphasic release pattern from HPMC/pectin /calcium matrix tablets
A binary polymer matrix tablet based on pectin / HPMC was developed earlier (Kim and Fassihi, 1996). Pectin is a naturally occurring polymer having high hydrophilicity. To overcome this high hydrophilicity, a novel approach of inducing cross linking in the pectin chains by using calcium was developed. Due to this cross linking of pectin a remarkable suppression in drug release, resulting in biphasic release pattern was noticed. Due to the initial release lag time shown by this system, it can be used for time or site specific drug delivery (Wu et al., 2007).
2.2.2 Recent novel approaches
Recently a number of approaches have been developed to achieve a zero-order or bi-modal release profiles from oral formulations.
These include the development of chitosan/carbopolinterpolymer complex (IPC) by precipitation method in acidic solution. Chitosan is a versatile semisynthetic polymer employed in various delivery systems (Dash et al., 2011).Diffusional release was observed from this system at neutral or basic pH whereas relaxational release at acidic pH.This IPC matrix system showed similar release patterns like that of HPMC (Park et al., 2006).
Another approach includes combination of cellulose ethers (MC, HPMC, and HPC) with naturally occurring class of polymers called carrageenans (iota, lambda and kappa carragenans). Most of the formulations in this class showed anomalous transport mechanism, whereas zero order release was also observed through few of them (Nerurkar, 2005).
In addition the release pattern from HPMC based matrix system with different degree of substitution (E4M, F4M, K4M) was modified using a new family of graft co-polymers of methyl acrylate. The underlying release mechanism for this blend of polymers is the combination of both diffusion and erosion (Escudero et al., 2009).
Another recently developed approach is Kollidon SR matrix system which comprises of a blend of polyvinyl acetate and polyvinylpyrrolidone. This system has a unique feature of maintaining its geometric shape resulting in a diffusion controlled release mechanism (Sakr et al., 2010).
PROPOSAL IDEA, INTENDED EXPERIMENTAL DESIGN AND INVESTIGATION METHOD
3.1 PROPOSED COMBINATION OF POLYMERS AND INTENDED MATRIX TABLET DESIGN
Present study proposes a design of multi-layer matrix tablet using a combination of two different polymers with an intention to achieve bimodal drug release. Different types of polymeric blends for hydrophilic matrices have been extensively reviewed and it was found that cellulose ethers are most commonly used for this purpose (Conti et al., 2006). There is a paucity of available options for hydrophilic matrices. This study makes an effort to develop an alternative polymer for cellulose ethers, which can give desired drug release profile.
Figure 7: Representation of the intended blend of polymers (PEO and Carrageenanas)
The polymer blend intended to be used is comprised of combination of polyethylene- oxide and carrageenans. No evidence of use of this combination has been found in previous literature. In a recent study, the high molecular weight PEO have found to successfully replace the widely used HPMC in multilayer Geomatrix tablets (Maggi et al., 1999). So PEO was chosen in combination with the carrageenans. Carrageenans are high molecular weight naturally occurring sulfated polysaccharides divided into three types:
The first one is lambda carrageenan, which does not gel but form viscous solutions whereas the second and third one iota and kappa carrageenan gel but does not dissolve in water (Nerurkar et al., 2005).
In this study three approaches will be considered to modulate drug release using combination of polymers.
1st approach: In this approach, a matrix tablet utilising a blend of PEO and carrageenans will be prepared. The effect of varying concentration of all the three types of carrageenans in combination with PEO in the matrix tablet (Tablet I) using ibuprofen as a drug model will be studied. Dissolution and swelling studies will be employed for this purpose.
2nd approach : With a aim to achieve bimodal drug release to suit the absorption variation in GI tract, a multilayer matrix tablet using the above prepared matrix tablet as core (Tablet I) is intended. The tablet core consisting of drug (ibuprofen) dispersed in matrix blend, will be coated with a barrier layer of PEO-carrageenans on one side (Tablet II) and on both sides (Tablet III).
3rdapproach: In a study carried out by Hardy et al., 2006 it is evident that, the drug release from HPMC matrix is modulated by simple incorporation of PVP resulting in bimodal release. This effect of PVP on modulation point of this blend of PEO and carrageenans will also be checked by incorporating PVP and preparing tablets using this blend (Tablet IV).
Figure 8: Three approaches (intended design) proposed to modulate drug release from hydrophilic matrices using a polymer combination
To study the release kinetics from this matrix, dissolution studies or HPLC will be performed. FT-NIR will be used to study the spatial distribution of components in this system. Cryogenic scanning electron microscopy is intended to be used for observing the changes in surface topography, swelling and erosion. By employing regression analysis the drug release at different time points will be observed. Using the values for release rate constant (k) and diffusional exponent (n), the release mechanism from this system will be characterised. Usually synchronisation of diffusion and erosion is found to be the underlying mechanism for swell able polymers (Nerurkar et al 2005).
After an extensive literature survey of relevant articles it was found that some of the polymer combinations like xanthan gum-carrageenans and xanthan gum PVP for hydrophilic oral extended release matrices based tablets have not been studied before. A similar study on these combinations can also be performed.
3.2 EXPERIMENTAL DESIGN
To achieve bimodal drug release with a multi-layer matrix tablet using a combination of polymers and to study the effect of PVP on modulation of drug release from this system.
To carry out a review of the previous and recent scientific literature covering the problem of modulation of drug release from hydrophilic matrices.
To propose a novel combination of polymers and to prepare a core matrix tablet formulation using this polymer blend and ibuprofen as model drug (Tablet I).
To design a multi-layer matrix tablet using this polymer blend to achieve bimodal drug release (Tablet II and III).
To study the effect of PVP on drug release from the core matrix tablet (Tablet IV).
To study the effect of viscosity, erosion and diffusion on modulation of drug release from all these formulationsusing various techniques like HPLC, FT-NIR, SEM (Tablet I, II, III and IV)
Ibuprofen, high molecular weight polyethylene oxide (Polyox WSR N60K, PEO), carrageenans (lambda, iota and kappa), polyvinylpyrrolidone (Plasdone K90, PVP), magnesium stearate.
Dissolution apparatus, Fourier transformation near infrared spectroscope (FT-NIR), scanning electron microscope (SEM), High performance liquid chromatography (HPLC).
126.96.36.199 Polymer blends and tablet preparation
Tablets will be prepared by using two combination polymers, A = Polyethylene oxide (PEO) and B = Carrageenan's (B1 = lambda, B2 = iota, B3 = kappa). Magnesium stearate (0.25-2%) will be used as lubricant. The amount of ibuprofen will be kept constant (100mg) and the concentration of polymers will be varied according to the ratios given in table (2). For 1st approach(Tablet I) core tablet,all the ingredients except lubricant will be mixed separately for about 15-20 min in a mixer and then again mixed after adding lubricant for about 2-3 min (Nerurkar et al., 2005). Tablets will be prepared by direct compression method using a single punch tableting machine. Compression aid will be added if required.
Table 2: Proposed formulations for 500mg core matrix tablet containing constant amount of ibuprofen (100 mg)
A = Polyethylene oxide (PEO), B = Carrageenans (B1 = lambda, B2 = iota, B3 = kappa)
For multi layered matrix tablet, Tablet II and III (approach 2), the die of single punch tablet machine will be progressively filled with the homogenous mixture of respective powder blends of each formulation. The barrier weight will be varied 60 to 100 mg so as to achieve proper thickness. This will be followed by compression.
For the 3rd approach (Tablet IV), 0, 0.5, 1, 2, 4, 6, 8, 10 % PVP will be incorporated into the blend of polymers listed in table 1 and the same procedure for tablet preparation will be followed.
The hardness of all the tablet formulations will be kept constant (80-100 N) (Streubel et al., 2000).
188.8.131.52 Standard physical tests of tablets
Variations in properties of prepared tablets will be tested using standard physical tests. Variation in weight of the tablets will be determined by taking the weight of 20 tablets using an electronic balance. The thickness of these tablets will be determined using a micrometer sample mean and standard deviation will be determined. The friability for 15 tablets will be determined using friability tester at 25 revolutions/min for 4 min (Ferrero et al., 1997).
184.108.40.206 Dissolution studies
Dissolution studies will be performed on designed matrix tablets using paddle method (USP) at 100 rpm and 37Â± 0.5ËšC. Simulated intestinal fluid (SIF) will be employed as dissolution medium. The amount of ibuprofen released will be determined by withdrawing 5 ml sample at specific time intervals. Concentration will be determined by measuring absorbance at 263 nm using UV spectrophotometer. Alternatively, HPLC will be employed to study the drug release pattern (Nerurkar et al., 2005).
220.127.116.11 Analysis of drug release kinetics
Exponential equation will be employed to study the release behaviour from this matrix system.
Where, Mt/Mn is the fraction of drug released at time t
k is proportionality constant (represents geometrical properties of matrix)
n is the exponent (depends upon swelling and relaxation rate)
Table 3: Variation of n values with drug release mechanism
Case II transport
Supercase II transport
(Conti et al., 2007)
Higher k values indicate burst drug release from matrix. This equation holds true only for early stages of drug release (â‰¤ 70% ) (Conti et al., 2007). This equation will be employed to study the drug release mechanism from the designed formulation.
18.104.22.168 Swelling and erosion studies
The tablets under investigation will be weighed and placed in a tared metallic basket. 900 ml of simulated intestinal fluid (SIF) will be employed for this test. The baskets will then be immersed in SIF and tested at 100 rpm and 37Â±0.5ËšC. At specific time intervals this baskets will be removed and excess water will be removed using tissue paper. This basket will then be weighed and the tablets will be dried under vaccum for 24 h. The degree of swelling and erosion will be calculated using these formulas (Park et al., 2008).
% degree of swelling = [(Ws-Wd) /Wd]Ã-100
Ws = weight of swollen matrix
Wd= weight of dry matrix
% degree of erosion = [(Wi - Wd) / Wi] Ã- 100
Wi= initial weight of the tablet
Wd= corrected weight by substracting buffer componenets
22.214.171.124 Viscocity measurements
The effect of viscosity of polymer blend on drug release through hydrophilic extended release matrices will be measured. Solutions of different concentrations (0.1, 0.2, 0.3, 0.4, and 0.5% w/v) of PEO, Carrageenans (lamda, iota and kappa) and their blends will be prepared in deionised water. Solutions will be stirred vigorously so as to disperse the polymers, prior to testing. Test will be performed using Brookfield viscometer at 37ËšC (Kim and Fassihi , 1996).
126.96.36.199 Effect of PVP on drug release from PEO
The effect of incorporating PVP on the release profile of ibuprofen from Polyethylene oxide and carrageenans blend will be studied. It is evident from recent study carried out by Hardy et al., 2007 that the PVP in critical concentrations modulate the drug release through HPMC matrix system by reducing the strength of gel structure. PEO-carrageenans system will be checked for this effect by incorporating varying amount (0, 0.5, 1, 2, 4, 6, 8, 10 %) of PVP in intented formulations given in table 1. Ibuprofen will be used as model drug. Employing dissolution studies and plotting % drug dissolved vs. time from the data obtained an idea of the release pattern from this system will be obtained. Thus this matrix tablet system can be checked for bimodal release pattern. Changes in surface morphology of this system will be studied using FT-NIR.
188.8.131.52 Scanning electron microscopy (SEM) and Fourier transformation - Near infrared microscopy (FT - NIR) studies
SEM and FT-NIR studies will be performed so as to allow detection and spatial mapping of individual components in sample.
SEM: For SEM analysis, the sample will be coated with gold palladium mixture and examined using accelerated voltage of 5 - 15 kV. To study changes in surface topography due to swelling and hydration, cryogenic SEM will be performed. The tablets will be hydrated for 24 h and then transferred to cryopep chamber by plunging in nitrogen slush. Hydrated tablets will be etched with liquid nitrogen for 2h and a dry tablet for 5-15 min and observed using Cryogenic SEM (Nerurkar et al., 2005).
FT-IR/FT-NIR: Samples will be hydrated using USP apparatus 1 containing 900 ml of de-ionised water at 37ËšC and 100 rpm. The hydrated sample will be deposited in freeze dryer tube which will be put into a CO2 ice and methanol bath. Once the temperature falls below -50ËšCand pressure below 13Pa vacuum water will be removed by sublimation. The sample will be kept for overnight drying when the pressure falls below 130 Pa. Samples will be taken at 2, 4 and 7 h for dry as well as hydrated tablets. The samples will then be micro tomed and observed under FT-IR/FT-NIR (Hardy et al., 2007).
The overall rate of drug (ibuprofen) release from the proposed matrix system can be modulated by monitoring the viscosity and thickness of gel layer formed. Thus, by blending polyethylene oxide and carrageenans (lambda, iota, kappa) and designing a two or three layered system by using this blend or by incorporating PVP in this blend a simple, economic and reliable system with bimodal release pattern will be achieved.