Carbopol 71G Research Articles

In Vitro and In Vivo Evaluation of Carbopol 71G NF-Based Mucoadhesive Minitablets as a Gastroretentive Dosage Form.

Gastroretentive dosage forms are intended to stay inside the stomach for a long period of time while releasing an active pharmaceutical ingredient. Such systems may offer significant benefits for numerous drugs compared to other sustained release systems, such as improved pharmacokinetics/bioavailability and reduced intake frequency and thereby improved adherence to the medical therapy. However, there is no gastroretentive product on the market with proven reliable gastroretentive properties in humans. A major obstacle is the motility pattern of the stomach in the fasting state in humans, which reliably ensures gastric emptying of even large indigestible objects into the small intestine. One promising approach to avoid gastric emptying is adhesion of the drug delivery system to the gastric mucosa. In order to achieve mucoadhesive properties, minitablets containing Carbopol 71G NF were developed and compared to minitablets without adhesive properties. In a specialized mucoadhesive test system, the adhesion time was prolonged for adhesive minitablets (240 min) compared to non-adhesive minitablets (30 min). The in vivo transit behavior was investigated using magnetic resonance imaging in 11 healthy volunteers in fasted state in a crossover setup. It was found that the gastric residence time (GRT) of the adhesive minitablets (median of 37.5 min with IQR = 22.5-52.5) was statistically significantly prolonged compared to the non-adhesive minitablets (median of 7.5 with IQR = 7.5-22.5), indicating a delay in gastric emptying by adhesion to the gastric mucosa. However, the system needs further improvement to create a clinical benefit. Furthermore, it was observed that for 9 of 22 administrations (three minitablets were given simultaneously with every administration), the minitablets were not emptied together but showed different GRTs.

FORMULATION AND IN-VITRO EVALUATION OF NICARDIPINE HYDROCHLORIDE BILAYERED TABLET FOR CONTROLLED RELEASE

The aim of present research work was to prepare and evaluate the controlled release bilayered tablet of Nicardipine HCL to improve its bioavailability for the treatment of hypertension. To minimize critical process parameters, two layer compression method was used for the formulation of Bilayered tablets. The appropriate formulation was achieved successfully with the combination of Polymers MCC, Carbopol 71G and HPMC K100M produced desired release profile for Metoprolol succinate extended release layer. The combination of disintegrating agents that is Sodium starch glycolate and Dicalcium phosphate produced desired release rate for Nicardipine immediate release layer. The results reveal that formulation F7 has met the objective of controlled drug release for over a period of 12 hrs. The formulation F7 ascertained the efficacy of the controlled released Bilayered tablet of Nicardipine and Metoprolol ER tablet in hypertension. This sustained release Bilayered tablet with the combination of Nicardipine and metoprolol can be used in the management of different types of hypertension. The formulation F7 of combination of Nicardipine and metoprolol showed controlled release profile among the other, Hence it was considered as an optimized formulation.

Development and Characterization of Barbaloin Gel for the Safe and Effective Treatment of Psoriasis

Psoriasis is an inflammatory skin disease which cause inflammation to the skin and generally the symptoms includes white or red colour of irregular skin; the patches are developed and they are commonly itchy and scaly to the skin. Barbaloin is an herbal phytoconstituent which is obtained from the plant aloe vera leaf part. In the present study hydrogels formulation batches from F1 to F10 were prepared by using carbopol 934, Xanthan gum, carbopol 940, and carbopol 71G NF as a gelling agent. The prepared formulations from F1 to F10 were evaluated for their physical appearance, Grittiness, spreadability, Homogeneity, viscosity, pH, swelling index and microscopical evaluation. The changes in each evaluation parameter were examined at multiples concentration of each polymer. The effects of gelling agent in each formulation were observed and it will help us to justify the suitable range of polymer as a single or in combination with other gelling agent. From these studies it was found to be formulation F2, F4, F7 and F10 showing good gelling properties and further these four formulations are selected for In Vitro drug release studies. By In Vitro drug release kinetics study formulation F2 and F10 showed higher release as compared to F4 and F7. Furthermore, formulation F2 and F7 had good kinetic release study and showed non fickian drug release as the n value was between 0.8-0.9. Therefore, from the above release study parameters formulation F2 and F10 show the best optimized release characterstics as compare to the selected optimized formulations F4 and F7.
 Keywords: Psoriasis, Barbaloin, Hydrogel, Formulation and Evaluation.

Comparative analysis of carbomer polymers for pharmaceutical and cosmetic practice

The aim of the study. Given the wide range of carbomers, their manufacturing technologies, solvent systems for their synthesis, differences in name and regulation, there is a need to systematize this group of excipients for the pharmaceutical and cosmetic industries. When using carbomers in the pharmaceutical development of medicines, the results of additional studies on the compliance of quality with pharmacopoeial indicators should be provided in registration materials.Materials and methods. As materials used were data from the official websites of the Ministry of Health of Ukraine, the FDA and Lubrizol; Pharmacopoeias of the United States (USP/NF), Europe (Ph. Eur) and Japan (JPE); scientific publications. Methods of information retrieval, systematization of theoretical and practical material were used.Results. As a result of studying the official regulatory documents it has been found that the US Pharmacopoeia (USP/NF) contains monographs called “Carbomer Copolymer”, “Carbomer Interpolymer” and “Carbomer Homopolymer”, which are classified into types A, B, C for polymers synthesized without the use of benzene, and monographs “Carbomer934”, “Carbomer 934Р”, “Carbomer940”, “Carbomer941”, “Carbomer1342” – for polymers synthesized using benzene. The Pharmacopoeia of Europe (Ph. Eur) contains a monograph “Carbomers” of a general nature, the requirements of which are met only in “Carbomer Homopolymer” polymers synthesized without the use of benzene by USP/NF. The Japan Pharmacopoeia (JPE) contains the monograph “Carboxyvinyl Polymer”, which includes carbomers synthesized both with and without benzene.Conclusions. The USP/NF pharmacopoeial quality requirements are met in the trademarks of carbomers: Carbopol 71G NF, Carbopol 971P NF, Carbopol 974P NF, Carbopol 980 NF, Carbopol 981 NF, Carbopol 5984 EP, Carbopol 934 NF, Carbopol 934P NF, Carbopol 940 NF, Carbopol 941 NF, Carbopol 1342 NF, Carbopol Ultrez 10 NF, Carbopol ETD 2020 NF, Pemulen TR-1 NF, Pemulen TR-2 NF, Noveon AA-1 USP. Only 6 brands of carbomers meet the requirements of the European Pharmacopoeia: Carbopol 71G NF, Carbopol 971P NF, Carbopol 974P NF, Carbopol 980 NF, Carbopol 981 NF, Carbopol 5984 EP.

Development and in vitro Characterization of Gastro Retentive Raft Forming Stavudine Tablets

The objective of the present investigation was to identify a suitable raft forming agent and to develop raft forming stavudine matrix tablets using different rate controlling natural, semi-synthetic and synthetic polymers to achieve prolonged gastric residence time, leading to an increase in drug bioavailability and patient compliance. Various raft forming agents were used in preliminary screening. Raft forming floating tablets were developed using pullulan gum as natural rate controlling polymer, and directly compressible grades of hydroxypropyl methylcellulose (Benecel K4M DC) as semi synthetic, and Carbopol 71G as synthetic rate controlling polymers respectively and optimum concentrations of sodium-bicarbonate as gas generating agent to generate optimum buoyancy by direct compression method. Raft forming tablets were evaluated for weight variation, thickness, hardness, friability, drug content, in vitro drug release, floating buoyancy and raft strength. Drug-excipients compatibility study showed no interaction between drug and excipients. Raft forming tablets showed satisfactory results when evaluated for weight variation, thickness, hardness, friability, drug content, and raft strength. The optimized formulation was selected based on physicochemical characteristics and in vitro drug dissolution characteristics. Further, the optimized formulation was evaluated for in vivo radiographic studies by incorporating BaSO4 as radio opaque substance. Optimized formulation showed controlled and prolonged drug release profiles while floating and raft formation over the dissolution medium. Diffusion followed by erosion with raft forming drug release mechanism was observed for the formulation, indicating that dissolution media diffusion and polymer erosion played an essential role in drug release. In vivo radiographic studies revealed that the raft forming formulations remained in the stomach for 240 30 min in rabbits and indicated that gastric retention time was increased by the floating and raft forming principle, which was considered and desirable for absorption window drugs.

Mucoadhesive amorphous solid dispersions for sustained release of poorly water soluble drugs

The oral delivery of mucoadhesive patches has been shown to enhance the absorption of large molecules such as peptides. We hypothesized that this mechanism could have utility for poorly soluble small molecules by utilizing a mucoadhesive polymer as the matrix for an amorphous solid dispersion. Binary dispersions of itraconazole and carbomer (Carbopol 71G) were prepared utilizing a thermokinetic mixing process (KinetiSol Dispersing) and the physicochemical properties were investigated by powder X-ray diffraction, calorimetry, and liquid chromatography. Adhesion of the dispersions to freshly excised porcine intestine was investigated with a texture analyzer. Minitablets were compressed from the optimal dispersion and further investigated in vitro and in vivo in rats. Thermokinetic mixing successfully processed amorphous dispersions up to 30% drug loading and each dispersion exhibited works of adhesion that were approximately an order of magnitude greater than a negative control in vitro. Ethylcellulose (EC) coated and uncoated minitablets prepared with the 30% drug load dispersion were delivered orally to rats and exhibited sustained release characteristics, with overall bioavailability greater for the uncoated minitablets compared to the EC-coated minitablets, similar to the rank order observed in our in vitro dissolution experiments. Necropsy studies showed that minitablets delivered with enteric-coated capsules targeted release to the distal small intestine and adhered to the intestinal mucosa, but the rat model presented limitations with respect to evaluating the overall performance. Based on the in vitro and in vivo results, further investigations in larger animals are a logical next step where fluid volumes, pH, and transit times are more favorable for the evaluated dosage forms.

Improved Skin Penetration Using In Situ Nanoparticulate Diclofenac Diethylamine in Hydrogel Systems: In Vitro and In Vivo Studies.

Delivering diclofenac diethylamine transdermally by means of a hydrogel is an approach to reduce or avoid systemic toxicity of the drug while providing local action for a prolonged period. In the present investigation, a process was developed to produce nanosize particles (about 10 nm) of diclofenac diethylamine in situ during the development of hydrogel, using simple mixing technique. Hydrogel was developed with polyvinyl alcohol (PVA) (5.8% w/w) and carbopol 71G (1.5% w/w). The formulations were evaluated on the basis of field emission scanning electron microscopy, texture analysis, and the assessment of various physiochemical properties. Viscosity (163-165 cps for hydrogel containing microsize drug particles and 171-173 cps for hydrogel containing nanosize drug particles, respectively) and swelling index (varied between 0.62 and 0.68) data favor the hydrogels for satisfactory topical applications. The measured hardness of the different hydrogels was uniform indicating a uniform spreadability. Data of in vitro skin (cadaver) permeation for 10 h showed that the enhancement ratios of the flux of the formulation containing nanosize drug (without the permeation enhancer) were 9.72 and 1.30 compared to the formulation containing microsized drug and the marketed formulations, respectively. In vivo plasma level of the drug increased predominantly for the hydrogel containing nanosize drug-clusters. The study depicts a simple technique for preparing hydrogel containing nanosize diclofenac diethylamine particles in situ, which can be commercially viable. The study also shows the advantage of the experimental transdermal hydrogel with nanosize drug particles over the hydrogel with microsize drug particles.

Formulation and In-Vitro Evaluation of In-lay Matrix Tablets Containing Telmisartan and Hydrochlorothiazide

The aim of the presented work was formulation and in-vitro evaluation of in-lay tablets containing telmisartan as sustained release outer core and hydrochlorothiazide as immediate release inner core using HPMC and copolymer carbopol 71G. Tablets were evaluated via various quality control tests and in-vitro drug release studies. Drug release study was carried out hydrochloric acid buffer of pH 1.2 (0.1N) using USP paddle apparatus. The validated HPLC-UV method was applied to determine the amount of drugs released at different time intervals. The mechanism of drug release through polymeric network was established. Prepared tablets showed extended sustain release of telmisartan over a period of 20 h and hydrochlorothiazide as immediate release within 30 min.

Formulation and evaluation of sustained release venlafaxine tablets using hydrophilic-hydrophobic polymer combinations by melt granulation

The current research aims to formulate Venlafaxine Sustained Release (VHL-SR) tablets using hydrophilic-hydrophobic polymers combination blends by melt granulation technique which highlights the novelty. The polymers selected for the present study have matrix forming properties. Results of FTIR studies have shown that there were no interactions between the polymers used and the drug VHL. Various formulations of VHL- SR tablets (F1-F16) using different combinations of hydrophilic and hydrophobic polymers viz. Carbopol 71G, HPMC K15M, PEO, sodium CMC, Eudragit RS100 and precirol were formulated. Prior preformulation studies carried out on powder blend showed good flow properties. Routine quality evaluations of the VHL-SR tablets showed the diameter of the tablets of all formulations were found to be 9.0±0.0 mm and thickness ranged between 2.08±0.08 to 2.25±0.14 mm, hardness 4.08±0.20 - 5.50±0.31 kg/cm2 , percentage friability 0.24±0.03 - 0.45±0.01%, weight variation from 0-1.15%, drug content uniformity from 98.17±0.68 to 101.89±0.73%, all within Pharmacoepial limits. Results of in-vitro drug release study indicated that the formulation containing Carbopol 71G (50 mg), Xanthan gum (75 mg) and MCC (50 mg) extended the release of the VHL. Formulation F15 was the optimized one which gave satisfactory release (95.2%) for 16 hr and with a similarity factor (f2) 68.46, the release kinetics best explained by the Korsmeyer-peppas and Higuchi diffusion models. The “N” values between 0.5-1.0 in all the formulations exhibiting a non-Fickian release behavior controlled by a combination of diffusion and chain relaxation mechanism. The formulation showed appreciable stability under accelerated conditions after 2 m.

Drug release profiles and microstructural characterization of cast and freeze dried vitamin B12 buccal films by positron annihilation lifetime spectroscopy

Solvent cast and freeze dried films, containing the water-soluble vitamin B12 as model drug were prepared from two polymers, sodium alginate (SA), and Carbopol 71G (CP). The proportion of the CP was changed in the films. The microstructural characterization of various samples was carried out by positron annihilation lifetime spectroscopy (PALS). The drug release kinetics of untreated and stored samples was evaluated by the conventionally applied semi-empirical power law.Correlation was found between the changes of the characteristic parameters of the drug release and the ortho-positronium (o-Ps) lifetime values of polymer samples. The results indicated that the increase of CP concentration, the freeze-drying process and the storage at 75% R.H. decreased the rate of drug release.The PALS method enabled the distinction between the micro- and macrostructural factors influencing the drug release profile of polymer films.

Formulation optimization of hot-melt extruded abuse deterrent pellet dosage form utilizing design of experiments

The objective of this study was to develop techniques for an abuse-deterrent (AD) platform utilizing the hot-melt extrusion (HME) process. Formulation optimization was accomplished by utilizing Box-Behnken design of experiments to determine the effect of the three formulation factors: PolyOx WSR301, Benecel K15M and Carbopol 71G; each of which was studied at three levels on tamper-resistant (TR) attributes of the produced melt extruded pellets. A response surface methodology was utilized to identify the optimized formulation. Lidocaine hydrochloride was used as a model drug, and suitable formulation ingredients were employed as carrier matrices and processing aids. All of the formulations were evaluated for the TR attributes, such as particle size post-milling, gelling and percentage of drug extraction in water and alcohol. All of the design of experiments formulations demonstrated sufficient hardness and elasticity, and could not be reduced into fine particles (<150 μm), which is a desirable feature to prevent snorting. In addition, all of the formulations exhibited good gelling tendency in water with minimal extraction of drug in the aqueous medium. Moreover, Benecel K15M, in combination with PolyOx WSR301, could be utilized to produce pellets with TR potential. HME has been demonstrated to be a viable technique with a potential to develop novel AD formulations.

Formulation development and in vitro and in vivo evaluation of gastroretentive floating drug delivery system of Lafutidine

Lafutidine a newly developed histamine H2‐receptor antagonist was retained in the stomach and assist in improving the oral sustained delivery of drugs in the gastrointestinal tract. A floating drug delivery system (FDDS) was developed using the gas forming agents, such as sodium bicarbonate, citric acid with hydrochlorides, such as hydroxyl propyl methyl cellulose (HPMCK 4M, HPMCK15M) and novel Carbopol 71G. Polymer with lower viscosity was found to be beneficial than higher viscosity polymer in improving the release properties of gastroretentive FDDS. The prepared tablets of various formulations were evaluated for a total floating time, buoyancy lag time, and percentage drug released.The formulation code HF3 having HPMCK4M showed better results it may be useful for prolonged drug release in the stomach to improve the bioavailability and reduced the dose frequency. Non‐Fickians release transport was confirmed as the drug release mechanism from the optimized formulation by Korsmeyer‐Peppas. In vivo study was per formed using the rabbits by X‐ray imaging technique; radiological evidences suggest that, a formulated tablet was well floated more than 10 h in rabbit’s stomach.Optimized floating tablets showed no significant changes in the physical appearance, drug content, total buoyancy time, and also in vitro dissolution pattern after storage at 40°C/75% relative humidity for 3 months.

Eudraginated polymer blends: A potential oral controlled drug delivery system for theophylline

Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for micromeritic properties, drug concentration and in vitro drug release. It was found that the in vitro drug release rate decreased with increasing the amount of polymer. Coating with EUD resulted in a significant lag phase in the first two hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to decreased water uptake, and hence decreased driving force for drug release. Release became faster in the alkaline pH of simulated intestinal fluid (SIF) owing to increased solubility of both the coating and matrixing agents. The optimized formulation was subjected to in vivo studies in rabbits and the pharmacokinetic parameters of developed formulations were compared with the commercial (Asmanyl(®)) formulation. Asmanyl(®) tablets showed faster absorption (t(max) 4.0 h) compared to the TPH formulation showing a t(max) value of 8.0 h. The C(max) and AUC values of TPH formulation were significantly (p < 0.05) higher than those for Asmanyl(®), revealing relative bioavailability of about 136.93 %. Our study demonstrated the potential usefulness of eudraginated polymers for the oral delivery of the sparingly soluble drug theophylline.

Real time positron annihilation lifetime spectroscopy for the detection of the hydrocolloid gel-film transition of polymers

Real time positron annihilation lifetime spectroscopy was applied to study the transition from hydrogel to film in the case of two biopolymer gels (sodium alginate and Carbopol 71G) of various concentrations (3 %w/w and 0.1–1 %w/w). The transition from a polymer-in-water system to a water-in-polymer system was sensitively tracked by o-Ps lifetime values as a function of the drying time. The addition of Carbopol 71G to the sodium alginate gel modified the phase transition time and, consequently, the drying characteristics of the gel, depending on its concentration. The developed method enabled the determination of the exact time needed for the gel-film transition. This could be of impact in the course of the formulation of hydrogel polymer delivery systems and coated dosage forms.

Effect of storage on microstructural changes of Carbopol polymers tracked by the combination of positron annihilation lifetime spectroscopy and FT-IR spectroscopy

Different types of Carbopols are frequently applied excipients of various dosage forms. Depending on the supramolecular structure, their water sorption behaviour could significantly differ. The purpose of the present study was to track the supramolecular changes of two types of Carbopol polymers (Carbopol 71G and Ultrez 10NF) alone and in their physical mixture with a water-soluble drug, vitamin B 12, as a function of storage time. The combination of FT-IR spectroscopy, positron annihilation lifetime spectroscopy (PALS) and Doppler-broadening spectroscopy was applied to follow the effect of water uptake on the structural changes. Our results indicate that water-induced interactions between polymeric chains can be sensitively detected. This enables the prediction of stability of dosage forms in the course of storage.

Effect of Kollidon® SR on the release of Albuterol Sulphate from matrix tablets

The objective of this study was to evaluate Kollidon SR for the development of extended release Albuterol Sulphate matrix tablets in comparison with other polymers as Hydroxypropylmethylcellulose K15M, Carbopol 71G NF, and Eudragit L100-55. The mechanical properties of the tablets were improved as concentration of Kollidon SR or other polymers increased. It was found that Kollidon SR 30% (w/w) and HPMC 30% (w/w) tablets have f 2 similarity factor of 83.5 in their Albuterol Sulphate dissolution profile. The marketed product was found to release 99.7% of drug content within 8 h, while Kollidon SR and HPMC tablets with 30% (w/w) polymer concentration level released 92.7% and 92.9% respectively of drug content within 8 h. Kollidon SR has a unique character of maintaining tablets geometric shape until the end of dissolution test, this is mainly due to the water insoluble content, polyvinyl acetate, forming 80% (w/w) of Kollidon SR, while the remaining content 20% (w/w) is the water soluble, polyvinylpyrrolidone, responsible for pore formation causing a diffusion controlled release. Drug release from all previous formulations is best described to be controlled by more than one kinetic mechanism of release. In conclusion, Kollidon SR and HPMC and Carbopol were found to be potential candidates for the development of extended release of Albuterol Sulphate tablets.

Influence of dissolution media composition on drug release and in-vitro/in-vivo correlation for paracetamol matrix tablets prepared with novel carbomer polymers.

The influence of dissolution media composition on drug release kinetics and in-vitro/in-vivo correlation (IVIVC) for hydrophilic matrix tablets based on Carbopol 971P and Carbopol 71G was investigated. A number of buffered and unbuffered media differing with respect to their pH value, ionic strength and ionic species was evaluated. The observed in-vitro drug release profiles were compared with the hypothetical drug release profiles in-vivo calculated by numerical deconvolution from the results of an in-vivo study. The obtained IVIVC plots were examined using linear and non-linear (proportional odds, proportional hazards and proportional reversed hazards) mathematical models. Although the studied sustained release agents were chemically identical, they exhibited pronounced differences in drug product behaviour both in-vitro and in-vivo. The use of non-linear modelling resulted in an improved level of correlation, especially in the case of Carbopol 71G matrices. The obtained results indicated the susceptibility of drug release kinetics and hence IVIVC in the case of anionic polymer matrices to media composition, and emphasized the need for thorough evaluation of applied media during the development of biorelevant dissolution methodology. Although the use of non-linear modelling could be advantageous, the need for a simple and meaningful non-linear relationship is pointed out.

Combining strategies to optimize a gel formulation containing miconazole: the influence of modified cyclodextrin on textural properties and drug release

Background: Miconazol, an antimycotic drug, is commonly formulated into semisolid formulations designed to be applied in the oral cavity to treat oral candidiasis. However, given its limited aqueous solubility, permeation through the biological membranes is low and therefore its activity is also limited. Cyclodextrins (CDs) have been widely used to increase the solubility and stability of poorly water-soluble drugs. Aim: The aim of this study is to formulate a gel containing an inclusion complex between a modified CD, methyl-β-cyclodextrin (MβCD), and miconazole (MCZ). The influence of the CD on the textural properties of the prepared gel and the drug release from formulation were evaluated. Methods: The gels were prepared using two polymers, Carbopol 71G and Pluronic F127, which were selected taking into account their bioadhesiveness and thermal-sensitive gelling properties, respectively. Texture profile analyses were performed at two different temperatures to ascertain the influence of the temperature on the gel texture properties. The in vitro MCZ release profiles from the prepared gel and the commercial gel formulations were evaluated and compared using modified Franz diffusion cells. Results: The addition of MβCD to the gel resulted in a decrease of the gel adhesiveness and firmness, and the MCZ release profile through f1 and f2 proved to be similar to the commercial product. Conclusions: A gel comprising miconazol in the form of an inclusion complex with MβCD showed suitable textural properties to be applied to the buccal mucosa. The MβCD enhanced the solubility of the MCZ in the gel formulation resulting in adequate in vitro drug release profiles.

Optimization of drug release from compressed multi unit particle system (MUPS) using generalized regression neural network (GRNN)

The purpose of this study was development of diclofenac sodium extended release compressed matrix pellets and optimization using Generalized Regression Neural Network (GRNN). According to Central Composite Design (CCD), ten formulations of diclofenac sodium matrix tablets were prepared. Extended release of diclofenac sodium was accomplished using Carbopol 71G as matrix substance. The process of direct pelletisation and subsequently compression of the pellets into MUPS tablets was applied in order to investigate a different approach in formulation of matrix systems and to achieve more control of the process factors over the principal response--the release of the drug. The investigated factors were X1-the percentage of polymer Carbopol 71 G and X2-crushing strength of the MUPS tablet. In vitro dissolution time profiles at 5 different sampling times were chosen as responses. Results of drug release studies indicate that drug release rates vary between different formulations, with a range of 1 hour to 8 hours of dissolution. The most important impact on the drug release has factor X1the percentage of polymer Carbopol 71 G. The purpose of the applied GRNN was to model the effects of these two causal factors on the in vitro release profile of the diclofenac sodium from compressed matrix pellets. The aim of the study was to optimize drug release in manner which enables following in vitro release of diclofenac sodium during 8 hours in phosphate buffer: 1 h: 15-40%, 2 h: 25-60%, 4 h: 35-75%, 8 h: >70%.

Application of Design of Experiments and Multilayer Perceptrons Neural Network in the Optimization of Diclofenac Sodium Extended Release Tablets with Carbopol 71G

The purpose of the study was to screen the effects of formulation factors on the in vitro release profile of diclofenac sodium from matrix tablets using design of experiment (DOE). Formulations of diclofenac sodium tablets, with Carbopol 71G as matrix substance, were optimized by artificial neural network. According to Central Composite Design, 10 formulations of diclofenac sodium matrix tablets were prepared. As network inputs, concentration of Carbopol 71G and the Kollidon K-25 were selected. In vitro dissolution time profiles at 5 different sampling times were chosen as responses. The independent variables and the release parameters were processed by multilayer perceptrons neural network (MLP). Results of drug release studies indicate that drug release rates vary between different formulations, with a range of 1 h to more than 8 h to complete dissolution. For two tested formulations there was no difference between experimental and MLP predicted in vitro profiles. The MLP model was optimized. The root mean square value for the trained network was 0.07%, which indicated that the optimal MLP model was reached. The optimal tablet formulation predicted by MLP was with 23% of Carbopol 71G and 0.8% of Kollidon K-25. Calculated difference factor (f(1) 7.37) and similarity factor (f(2) 70.79) indicate that there is no difference between predicted and experimentally observed drug release profiles for the optimal formulation. The satisfactory prediction of drug release for optimal formulation by the MLP in this study has shown the applicability of this optimization method in modeling extended release tablet formulation.