Immediate Release Layer Research Articles

Development, Physicochemical Characteristics and Pharmacokinetics of a New Sustained-Release Bilayer Tablet Formulation of Tramadol with an Immediate-Release Component for Twice-Daily Administration.

There are some potential concerns about the currently marketed solid oral dosage forms of tramadol, including decreased adherence to immediate-release (IR) formulations due to the high number of doses taken each day and the slow rise in the blood tramadol concentration after administration of sustained-release (SR) formulations, which may not achieve a rapid analgesic effect. To overcome these potential concerns, a twice-daily double-layered tablet formulation of tramadol comprising IR and SR layers was developed. This article reports studies that assessed its physicochemical and pharmacokinetic properties. Dissolution tests of five bilayer tablet formulations (designated tablets A-E) and pharmacokinetic studies of tablets A and B were conducted to investigate the appropriate ratio of the IR/SR layers in the double-layered tablet. Additionally, pharmacokinetic studies of three finished dosage formulations (tablets C-E) were performed in healthy adult males to investigate the effect of food intake on drug absorption. Adjusting the excipients and tramadol content in the IR and SR layers of tablets A-E altered their dissolution profiles in a manner that could be predicted based on their compositions. The IR layer was released within 15min, and the SR layer was slowly released over 10h. In the pharmacokinetic study, the time to maximum plasma concentration (tmax) of tramadol after administration of tablets A (IR:SR: 20:80mg) and B (40:60mg) was shorter than that of a commercially available SR tablet, and the half-life (t1/2) was longer than that of a commercially available IR tablet. For tablets C-E, administration after food did not affect the area under theconcentration-time curve (AUC) or maximum drug concentration (Cmax) of tramadol, but the tmax was prolonged by about 1 h compared with administration in fasting conditions. The mean ± standard deviation tmax and t1/2 for tablet D (IR:SR: 35:65 mg) in the fasting condition was 1.09 ± 0.56h and 7.82 ± 0.85h, respectively. The respective values in the fed condition were 2.47 ± 1.06h and 7.12 ± 0.85h, respectively. To address the potential concerns regarding existing formulations of tramadol, a twice-daily, extended-release bilayer formulation of tramadol consisting of an IR and SR layer was developed. Pharmacokinetic studies confirmed that the plasma tramadol concentration increased quickly after administration and was maintained over a long period of time.

Development of a Bilayer Tablet by Fused Deposition Modeling as a Sustained-Release Drug Delivery System.

Three-dimensional printing by fused deposition modeling (FDM) coupled with hot-melt extrusion (HME) is a point of convergence of research efforts directed toward the development of personalized dosage forms. In addition to the customization in terms of shapes, sizes, or delivered drug doses, the modulation of drug release profiles is crucial to ensure the superior efficacy and safety of modern 3D-printed medications compared to those of conventional ones. Our work aims to solidify the groundwork for the preparation of 3D-printed tablets that ensure the sustained release of diclofenac sodium. Specifically, we achieved the fast release of a diclofenac sodium dose to allow for the prompt onset of its pharmacological effect, further sustaining by the slow release of another dose to maintain the effect over a prolonged timeframe. In this regard, proper formulation and design strategies (a honeycomb structure for the immediate-release layer and a completely filled structure for the sustained-release layer) were applied. Secondarily, the potential of polyvinyl alcohol to function as a multifaceted polymeric matrix for both the immediate and slow-release layers was explored, with the objective of promoting the real-life applicability of the technique by downsizing the number of materials required to obtain versatile pharmaceutical products. The present study is a step forward in the translation of HME-FDM-3DP into a pharmaceutical manufacturing methodology.

Formulation of Modified-Release Bilayer Tablets of Atorvastatin and Ezetimibe: An In-Vitro and In-Vivo Analysis.

The objective of this work was to formulate co-loaded bilayer tablets containing ezetimibe (EZB) and atorvastatin (ATC). ATC loaded in the immediate-release (IR) layer is an HMG CoA reductase inhibitor, while EZB, added in the sustained-release (SR) layer, is a lipid-lowering agent. This study was conducted to evaluate the effects of polymer on the formulation and characterization of bilayer tablets, as well as the therapeutic impact of the concurrent use of both drugs having a sequential release pattern. To obtain the optimized results, four different formulations with variable compositions were developed and evaluated for different parameters. The drug release studies were carried out using a type II dissolution apparatus, using phosphate buffer solution (PBS) of 1.2 pH for IR of EZB for an initial 2 h, followed by 24 h studies for ATC in PBS 6.8 pH. The IR layer showed rapid drug release (96%) in 2 h, while 80% of the ATC was released in 24 h from the SR layer. Locally obtained, 6-week-old female albino rats were selected for in vivo studies. Both preventive and curative models were applied to check the effects of the drug combination on the lipid profile, atherosclerosis and physiology of different organs. Studies have shown that the administration of both drugs with different release patterns has a better therapeutic effect (p < 0.05), both in preventing and in curing hyperlipidemia. Conclusively, through the sequential release of ATC and EZB, a better therapeutic response could be obtained.

Tailoring of Rosuvastatin Calcium and Atenolol Bilayer Tablets for the Management of Hyperlipidemia Associated with Hypertension: A Preclinical Study

Hyperlipidemia is still the leading cause of heart disease in patients with hypertension. The purpose of this study is to make rosuvastatin calcium (ROS) and atenolol (AT) bilayer tablets to treat coexisting dyslipidemia and hypertension with a single product. ROS was chosen for the immediate-release layer of the constructed tablets, whereas AT was chosen for the sustained-release layer. The solid dispersion of ROS with sorbitol (1:3 w/w) was utilized in the immediate-release layer while hydroxypropyl methylcellulose (HPMC), ethylcellulose (EC), and sodium bicarbonate were incorporated into the floating sustained-release layer. The concentrations of HPMC and EC were optimized by employing 32 full factorial designs to sustain AT release. The bilayer tablets were prepared by the direct compression method. The immediate-release layer revealed that 92.34 ± 2.27% of ROS was released within 60 min at a pH of 1.2. The second sustained-release layer of the bilayer tablets exhibited delayed release of AT (96.65 ± 3.36% within 12 h) under the same conditions. The release of ROS and AT from the prepared tablets was found to obey the non-Fickian diffusion and mixed models (zero-order, Higuchi and Korsmeyer–Peppas), respectively. Preclinical studies using rabbit models investigated the impact of ROS/AT tablets on lipid profiles and blood pressure. A high-fat diet was used to induce obesity in rabbits. Bilayer ROS/AT tablets had a remarkable effect on decreasing the lipid profiles, slowing weight gain, and lowering blood pressure to normal levels when compared to the control group.

Integration of lornoxicam nanocrystals into hydroxypropyl methylcellulose-based sustained release matrix to form a novel biphasic release system

The study aims to (a) enhance the solubility of a poorly soluble drug by optimization of nanocrystal formulation using the top-down approach and (b) modify the release profile of this drug, which exhibits a short elimination half-life, by the integration of a fast-release phase containing the optimized nanocrystals and a sustained-release phase in a compression-coated tablet. Nanocrystals of the model drug (lornoxicam; LNX) was prepared by simultaneous application of jet-milling and ball-milling techniques. Investigation of the precipitation inhibition capacity, thermal property, and interaction of different polymers with the drug revealed polyvinyl pyrrolidone K30 (PVP) as the most effective stabilizer for nanocrystals. The immediate-release layer containing the optimized nanocrystals (size of 279.5 ± 11.25 nm and polydispersity index of 0.204 ± 0.01) was then compressed on a zero-order sustained-release matrix core using different derivatives of hydroxypropyl methylcellulose (HPMC). Application of the Design of Experiment approach (DoE) was applied to optimize the formulation of tablet. Analysis of drug concentration in dog plasma by liquid chromatography-tandem mass spectrometry demonstrated an improvement in the release behavior of LNX from the optimal compression-coated tablet integrating a HPMC-based sustained release matrix core and a PVP-stabilized lornoxicam nanocrystals coating layer compared to the reference product.

Design and evaluation of in vivo bioavailability in beagle dogs of bilayer tablet consisting of immediate release nanosuspension and sustained release layers of rebamipide

The purpose of this study was to develop a once-daily, bilayer matrix tablet with immediate (IR) and sustained release (SR) layers of poorly water-soluble and absorption site dependent rebamipide (RBM) to substitute three times a day IR tablet. Owing to the pH-dependent poor water solubility of RBM in low pH condition, salt-caged nanosuspensions (NSPs) consisting of RBM and poloxamer 407 (POX 407) or poloxamer 188 (POX 188) were prepared using an acid-base neutralization method to increase the dissolution rate, which was subsequently applied to the immediate-release (IR) layer. Polyethylene oxide (PEO) with different molecular weights (PEO 100,000 and PEO 5,000,000) and hydroxypropyl methylcellulose 4000 (HPMC 4000) were then investigated as SR agents to incorporate into the SR layer with pure RBM via wet granulation method. The dissolution profile of the optimized bilayer tablet having 50% IR and 50% SR layer of 300 mg RBM showed that the IR layer could rapidly disintegrate in pH 1.2 buffer solution within 2 h, reaching 50% of drug release from the tablet, followed by an extended drug release from the SR layer in pH 6.8 buffer over 24 h. An in vivo pharmacokinetic study was carried out in beagle dogs to compare the optimal formulation (300 mg RBM bilayer tablet) and the commercial tablet (Mucosta® 100 mg) as a reference. Unexpectedly, despite enhanced dissolution rate in a controlled manner, a designed bilayer tablet had no dose- and dosage form dependent in vivo bioavailability in beagle dogs as compared with IR 100 mg RBM reference tablet. It was evident that solubility in low pH condition, gastric residence time and absorption site of RBM should be carefully considered for designing specific SR or gastroretentive dosage form to improve therapeutic outcomes.

Preparation and Bio Pharmaceutical Evaluation of Chrono Pharmaceutical Drug Delivery System of Atenolol

A time-adjustable pulsatile release system containing atenolol as an active pharmaceutical agent was developed for bedtime dosage administration and release of medicine in the early morning to manage elevated blood pressure. The system contained an immediate release (IR) core, a sustained-release (SR) plug, and a mucoadhesive cup layer and it was designed by the cup and core technique. The immediate-release layer was composed of atenolol, croscarmellose sodium, microcrystalline cellulose (MCC), sorbitol, talc, and magnesium stearate. The SR plug was composed of hydroxyl propyl methylcellulose (HPMC), polyvinyl pyrrolidine (PVP), MCC, Lactose, talc, and magnesium stearate. The mucoadhesive cup contains polycaprolactone and mucoadhesive polymer chitosan. Bilayer tablets were punched by applying different compressive forces. Based on the Release data of the drug from each layer F5 and S5 were selected for the preparation of the bilayer tablet. Cup composition containing 3% of chitosan provided the highest mucoadhesion time up to 10h. Pulsatile delivery of the drug from the formulation was observed at 300 min after the administration of the drug. The constructed pulsatile delivery systems were compared to that of commercially available atenolol IR tablet. The comparison demonstrated that the formulation is suitable for the intended chronopharmaceutical delivery of antihypertensive drugs. Keywords: Chronopharmaceuticals, Pulsatile Drug Delivery, Hypertension, Mucoadhesive Polymer, Atenolol

Characterization of bilayered matrix-type mucoadhesive buccal films containing tizanidine hydrochloride and piroxicam

Purpose: To formulate and characterize tizanidine hydrochloride (TZN) and piroxicam (PRX)-loaded bilayer mucoadhesive buccal films with an intention to improve the bioavailability and patient compliance in pain management.Methods: Bilayer buccal films were prepared by solvent evaporation technique using hydroxypropyl methylcellulose (HPMC) 15cps and polyvinylpyrrolidone (PVP K30 as immediate release (IR) layer forming polymers and HPMC K15 M, PVP K 90 along with various muco adhesive polymers (Carbopol P934, sodium alginate, etc), as sustained release (SR) layer forming polymers. The prepared films werecharacterized for thickness, weight variation, folding endurance, surface pH, swelling index,mucoadhesive strength, in vitro residence time, in vitro drug release, ex vivo permeation and drug release kinetics.Results: The prepared films were of largely uniform thickness, weight and drug content. Moisture loss (%) and folding endurance were satisfactory. Surface pH was compatible with salivary fluid. Disintegration time was 85 s for F1 and 115 s for F2 of IR films. In vitro dissolution studies showed 99.12 ± 1.2 % (F1) and 90.36 ± 1.8 % (F2) were released in 45 min. Based on the above results, F1 was chosen as the optimum formulation to be combined with SR layer of TZN. Amongst the SR layers of TZN in vitro drug release. The findings show that of F2 was 98.38 ± 0.82 % and correlated with ex vivo release. Drug release followed zero order release kinetics and mechanism of drug release was non-Fickian type diffusion. In vitro residence time was greater than 5 h.Conclusion: The findings show that the bilayer buccal films demonstrate the dual impact of deliveringPRX instantly from the IR layer, with good controlled release and permeation of TZN from the SR layer, thus providing enhanced therapeutic efficacy, drug bioavailability and patient compliance.

Development of a Robust Control Strategy for Fixed-Dose Combination Bilayer Tablets with Integrated Quality by Design, Statistical, and Process Analytical Technology Approach.

Control strategy and quality by design (QbD) are widely used to develop pharmaceutical products and improve drug quality; however, studies on fixed-dose combination (FDC) bilayer tablets are limited. In this study, the bilayer tablet consisted of high-dose metformin HCl in a sustained-release layer and low-dose dapagliflozin l-proline in an immediate-release layer. The formulation and process of each layer were optimized using the QbD approach. A d-optimal mixture design and response surface design were applied to optimize critical material attributes and critical process parameters, respectively. The robust design space was developed using Monte Carlo simulations by evaluating the risk of uncertainty in the model predictions. Multivariate analysis showed that there were significant correlations among impeller speed, massing time, granule bulk density, and dissolution in the metformin HCl layer, and among roller pressure, ribbon density, and dissolution in the dapagliflozin l-proline layer. Process analytical technology (PAT) was used with in–line transmittance near-infrared spectroscopy to confirm the bulk and ribbon densities of the optimized bilayer tablet. Moreover, the in vitro drug release and in vivo pharmacokinetic studies showed that the optimized test drug was bioequivalent to the reference drug. This study suggested that integrated QbD, statistical, and PAT approaches can develop a robust control strategy for FDC bilayer tablets by implementing real-time release testing based on the relationships among various variables.

Formulation and Evaluation of Bi-Layer Tablets of Ketorolac Tromethamine

The objective of the present study was to develop and evaluate bi-layer tablets of Ketorolac tromethamine, a nonsteroidal antiinflammatory drug with short half-life, that are characterized by initial burst drug release in the stomach and comply with the release requirements of sustained-release products. Each of the proposed bi-layer tablets is composed of an immediate-release layer and a sustained-release layer, anticipating rapid drug release that starts in the stomach to rapidly alleviate the symptoms and continues in the intestine to maintain protracted analgesic effect. Gastro retentive Bi-Layer tablets of Ketorolac Tromethamine were prepared by using hydrophilic polymers with direct compression on floating – matrix technology and evaluated. Ketorolac tromethamine is freely soluble in water, so it is suitable to develop it as gastro retentive bi-layer tablets using hydrophilic polymers. The developed formulation is equivalent to calculated theoretical drug profile in view of its in vitro release. Immediate release layer was prepared by using dry granulation method in which ac-di sol used as a disintigrant for immediate release of drug. Sustained release layer formulated by using HPMC as release retardant, two grades of HPMC that are HPMC K4M and HPMC K100M used to get sustained release profile for 24 hr. Various trial batches are taken to get desired release profile. Ketorolac tromethamine release from the developed floating formulation followed Higuchi model and nonFickian diffusion is found to be the main mechanism of drug release. The manufacturing procedure was found to be reproducible and formulations were stable after one month of stability studies.&#x0D; Keywords: FTIR; Gastro retentive bilayer; ketorolac tromethamine; in vitro release; stability; higuchi.

Analysis on the evaluation of aceclofenac bilayer tablets and its formulation using FT-IT method

The detached of the current research progress a bilayer tablet of aceclofenac utilizing sodium starch glycolate (SSG) and croscarmellose sodium (CCS) as super disintegrants for the formulation of immediate-release layer whereas polymers such as methocel K15M, Lubrizol 971P were utilized by the formulation of sustaining layer. The tablets were equipped by straight density technique. The organized tablets were estimated for pre-compressed parameters like micromeritic properties and post compressed parameters like bulk variation, aceclofenac satisfied and in-vitro dissolution studies. The in-vitro dissolution studies showed about 86.78 % of aceclofenac release from the bilayer tablet, indicating that a preliminary burst release of aceclofenac followed by sustaining action up to 12 h by the sustained layer of the tablets. In-Vitro kinetic data revealed that all the formulations surveyed the Higuchi prototype via fickian dispersal as announcement device subsequently the preliminary rupture announcement. FT-IR studies exposed here is no communication among the drug and polymers utilized in the study. The errand of medication is to safeguard and reestablish wellbeing and to soothe languishing. In this context, the most commonly used pain-relieving agent is aceclofenac an NSAID. In the present investigation, aceclofenac bilayer tablets were prepared to provide sustain effect for better therapeutic effect. These points of interest, clarify the requirement for the planning of changed medication conveyance framework.

A Controlled Release Theophylline Delivery System Based on a Bilayer Floating System.

Bilayer floating drug delivery is an approach that helps to overcome the shortcomings of single-layered tablets. There is little or no fluctuation of the drug in the blood stream or tissue, while control is enabled over the time and site of drug release. In the current study, bilayer theophylline matrix tablets were formulated by double compression and evaluated using granules produced by polymeric granulation and simple coacervation techniques. Bilayer floating theophylline tablets containing an immediate release layer (IRL) and a sustained release layer (SRL) were prepared. Granules for the IRL section were produced by wet granulation, while those for the SRL section were produced by polymeric granulation and simple coacervation techniques using Eudragit RL100 and carboxymethyl cellulose (CMC) as binder. The resulting granules were characterized for flowability and packing properties. Granules with adequate flow were compressed into flat-faced tablets 12 mm in diameter using a single punch tableting machine at an arbitrary load of 28 kgF on a load scale. The tablets were evaluated for hardness, weight variability, disintegration, friability, swelling index, floating time, and in vitro drug release. The angle of repose and Hausner ratio were 29.07±0.330 to 40.08±0.660 and 1.07±0.01 to 1.28±0.01, respectively. Tablets hardness values ranged from 4.74±0.36 to 9.84±0.49 kgF, while percentage friability ranged from 0.5% to 1.51%. Floating lag time was between 1±0.41 and 9±0.71 min, while the total floating time was between 1 min and 9 h. Over 50% of the drug was released within 7 h. Drug release from the tablets showed a prompt release phase and an extended release phase. Therefore, appropriate combination of Eudragit and CMC and the right reagent can produce well retarded bilayer floating tablets.

Use of Eudragit RS PO, HPMC K100M, Ethyl Cellulose, and Their Combination for Controlling Nicorandil Release from the Bilayer Tablets with Atorvastatin as an Immediate-Release Layer

To develop a bilayer tablet containing sustained-release (SR) nicorandil and immediate-release (IR) atorvastatin components in separate layers for the effective treatment of angina accompanied by hyperlipidemia with less dosing frequency and improved patient compliance. Sustained-release nicorandil layer was formulated using HPMC K100M with or without Eudragit RS PO and Ethyl Cellulose 10FP. An immediate-release atorvastatin layer was developed using crospovidone and sodium carbonate. The formulations were optimized using a central composite design with the help of Design Expert software. The bilayer tablets were manufactured using a double-compression technique. Dissolution test study was conducted using three different media (pH 1.2, 4.5, and pH 6.8 buffers). Dissolution profiles were analyzed through model-dependent and model-independent methods using DDSolver, an Excel-based add-in program. Selected formulations were subjected to accelerated stability study according to ICH guidelines. The bilayer tablets were successfully developed with desired quality attributes. Nicorandil release kinetics followed anomalous diffusion, and in vitro release profile was best expressed through the Higuchi equation, while atorvastatin release exhibited Weibull kinetics. The shelf-life of optimized formulations was found to be about 13 months. The combination of ethyl cellulose and HPMC K100M successfully controlled the release of nicorandil from the bilayer tablet containing immediate-release atorvastatin. The formulation can be subjected to pharmacokinetic studies and clinical trials in the future for better management of cardiovascular diseases and enhancing patient compliance.

Formulation and Evaluation of Biphasic Gastro Floating Tablets of Nateglinide and Atenolol

The aim was to design, formulate, and evaluate bilayer gastro floating tablets of an antidiabetic agent, nateglinide (immediate-release layer), and antihypertensive agent, atenolol (sustained-release layer). The solubility of model drug nateglinide was enhanced by using cremophor RH 40 and characterized by FTIR, DSC, XRD, SEM, and in vitro dissolution. It was found that selected ingredients were compatible, and crystalline nateglinide transits to an amorphous state. The gastro-bilayer tablets were directly compressed using the optimized nateglinide (solid dispersion equivalent to 60 mg of nateglinide) immediate-release layer (IRL2) containing different percentage of F-Melt type C and crospovidone and atenolol (50 mg) sustained-release layer (SRL6) using different percentage of HPMC K15, sodium bicarbonate, and MCC. Developed tablets were evaluated and found within the acceptance range as per the guidelines. The release of nateglinide and atenolol from an optimized bilayer tablet (BLT3) was 100 % within 60 min and 12 h, respectively. The floating lag time and total floating time were 2 min and 12 h, respectively. The atenolol sustained-release followed the diffusion mechanism. The combination of nateglinide and atenolol was successfully showed a biphasic release pattern. This formulation may strengthen the fixed-dose combination therapy for diabetes and hypertension at a low cost.

Formulation and evaluation of gastro-retentive floating bilayer tablet for the treatment of hypertension

The paper aimed to progress an ideal gastro retentive drug delivery system intended for directing Losartan and Hydrochlorothiazide as a fixed-dose combination for anti-hypertensive therapy. The bilayer tablets were primed through direct compression method. Losartan was formulated by means of a floating layer expending hydrophilic swellable polymer Hydroxy Propyl Methyl Cellulose K4M, ethyl cellulose (4cps) as a buoyancy enhancer, sodium bicarbonate as a gas spawning agent. The amount of polymer blends remains optimized using 23 full factorial designs. The clout of experimental factors such as swelling agent concentration, buoyancy enhancer and gas generating agent on floating lag time, total floating time, T50% and % drug release remain investigated to get optimized formulation. The responses remain analyzed using Analysis of variance, and polynomial equation stood created for every retort using Multiple linear regression analysis. Entirely preparations floated for more than 12 h. The release pattern of losartan stood fitted to diverse models based on the coefficient of correlation (r). All the formulations, except F2, showed the Korsemeyer-Peppas model as the best fit model. Formulation F2 showed the zero-order model. Diffusion exponents (n) remained indomitable designed for entirely formulations (0.45–0.89), accordingly the chief drug discharge mechanism was non-fickian (anamolous) transport. Formulation F4 containing 20% w/w Hydroxy Propyl Methyl Cellulose K4M, 15% Sodium bicarbonate and 5% ethyl cellulose (4cps) was the best formulation as per the range of drug release remain institute to be more than 95 % in 12h and floating lag time was 20.15 s. The immediate-release layer stood optimized using crospovidone and Indion 414 as a super disintegrant. Formulation A8 containing 2% Indion 414 was considered as optimized formulation as it released 99% drug within 35 min and possessed less disintegration time. Optimized formulation F4 from the controlled-release layer and A8 from immediate-release layer was used to formulate bilayer tablet. The optimized formulation was imperilled to stability reading for three months at 40○C/75% relative humidity. The stability revision exhibited no substantial alteration in the appearance of tablets, floating characteristics, drug content and in-vitro drug dissolution. Consequently, a biphasic drug release design was effectively accomplished over the formulation of floating bilayer tablets.

PART I: OPTIMIZATION OF HYDRALAZINE HYDROCHLORIDE IMMEDIATE RELEASE LAYER IN ANTIHYPERTENSIVE BILAYER TABLET

Objective: Aim of the present study was the optimization of the immediate release (IR) layer containing hydralazine hydrochloride (HHC) 25 mg and compressed with a sustained-release (SR) layer of isosorbide dinitrate (ISDN) 40 mg to decrease the dosing frequency.&#x0D; Methods: In this study, Drug-excipients compatibility study was carried out by FT-IR and a preliminary trial was conducted for screening of super disintegrating agents. The amount of sodium starch glycolate (SSG) (X1) and the amount of ac-di-sol® (X2) was chosen as independent variables in 32 full factorial design while wetting time (WT) (Y1), disintegration time (DT) (Y2) and In vitro drug release at 15 min (Q15) (Y3) were taken as dependent variables. Multiple linear regression analysis, ANOVA, and graphical representation of the influence of factor by 3D plots were performed by using sigma plot 13.0. In the present study, the following constraints were used for the selection of an optimized batch: WT&lt;16 s, DT&lt;25 s, and Q15&gt;90%. To validate the evolved mathematical models, a checkpoint batch was selected from its desirability value.&#x0D; Results: FT-IR spectra show that the drug and excipients were compatible with each other. The calculated F values found for WT, DT, and Q15 were 045.559, 077.100 and 278.760, respectively. All Calculated F values are greater than tabulated values for all dependent variables. Prepared checkpoint was selected from its desirability value 0.935 and it gives a 100% drug release within 30 min.&#x0D; Conclusion: These results confirm that the prepared HHC 25 mg IR layer is used for rapid control of hypertension.

DEVELOPMENT OF BILAYER TABLETS OF LOSARTAN POTASSIUM AND METFORMIN HYDROCHLORIDE LAYER USING NATURAL GUMS AS POLYMERS

Objective: The aim of this research work was to develop and evaluate a bilayer formulation of losartan potassium and metformin hydrochloride for the treatment of diabetic patients with hypertension. In the present study, losartan potassium as immediate-release (IR) layer and metformin hydrochloride as a sustained-release (SR) layer were selected.&#x0D; Methods: The polymers selected were fenugreek gum, sweet potato starch, and ispaghula gum as natural disintegrants for IR layer and guar gum, xanthan gum, and pectin for SR layer. Bilayer tablets were developed by employing the two layers.&#x0D; Results: For IR layer, L4 formulation with 5% ispaghula gum as natural disintegrant showed 98.94% drug release was selected as an optimized layer. For sustained layer, F2 formulation with 18.75% guar gum as drug retardant showed 97.17% drug release was selected as optimized layer. Optimized formulation followed zero-order kinetics. When the release data was plotted into Higuchi and Korsmeyer-Peppas equations, then it was confirmed that the optimized formulation exhibited a Fickian diffusion type drug release.&#x0D; Conclusion: Tablets prepared with 5% ispaghula gum and 18.75% guar gums as drug retardants were found to be useful for bilayer tablet formulation with desired drug release characteristics.

BILAYER TABLET TENDERED IMMEDIATE RELEASE OF PARACETAMOL AND SUSTAINED RELEASE OF IBUPROFEN FOR QUICK ONSET OF ACTION AGAINST PAIN AND FEVER

Objective: The objective of this research was to formulate bi-layer tablet which contains immediate-release layer of Paracetamol for quick onset of action and sustained release of Ibuprofen for prolonging long period.&#x0D; Materials and Methods: The following chemicals were used: Paracetamol (Combiotic Global Pvt. Ltd., India), Ibuprofen (Combiotic Global Pvt. Ltd., India), microcrystalline cellulose (MCC) (Avicel), and Polyvinylpyrrolidone (PVP) K-30 (Loba Chem). Wet granulation method was adapted to formulate the bilayer tablets. The immediate-release layer of Paracetamol was prepared using sodium starch glycolate as superdisintegrants, MCC as diluent, starch as binder. The sustained release layer of Ibuprofen was prepared using high-performance liquid chromatography E50LV and ethyl cellulose as binder along with other excipients such as MCC, PVP, and magnesium stearate by wet granulation technique.&#x0D; Result and Discussion: The release rate of Paracetamol from Formulations 1 was more than 80% at 40 min. In case of Ibuprofen, sustained-release polymers such as HPMC E50 LV were used to increase the release time.&#x0D; Conclusion: The bilayer tablets were prepared and show good release rate.

Bilayer Tablet: Novel Technology Use in Extended Release Drug Delivery System

Bilayer tablet is a successful technology of controlled release formulation or extended release formulation to provide successful drug delivery. The name of this development is clear that the tablets have been consisting of two layers, these are immediate release layer (IR) and another is extended release layer (ER). In this era it is very useful in many developing countries as a combination therapy for various disease treatment purposes. Bilayer tablet are needs to separate incompatible active pharmaceutical ingredients (API) by physical separation. In this formulation IR and ER both layers are present and it form extended release layer (ER). This types of formulations helps to maintain plasma level concentration in the body. So, it is a very useful and successful technology in novel drug delivery system. Keywords: Bilayer tablet, extended drug release, Tablet press,

Preparation, Characterization and Pharmacokinetics Evaluation of the Compound Capsules of Ibuprofen Enteric-Coated Sustained-Release Pellets and Codeine Phosphate Immediate-Release Pellets.

The objective of this study was to prepare ibuprofen enteric-coated sustained-release pellets (IB-SRPs) and codeine phosphate immediate-release pellets (CP-IRPs) to play a synergistic role in analgesia. The pellets were developed by extrusion-spheronization and fluidized bed coating technology. The single-factor investigation was used to determine the optimal prescription and process. The sustained-release membrane of IB-SRPs was water-insoluble ethyl cellulose (EC), triethyl citrate (TEC) was used as plasticizer, and hydroxypropyl methylcellulose (HPMCP) was chose as porogen. Besides, the immediate-release layer of CP-IRPs was gastric-soluble coating film. The ibuprofen and codeine phosphate compound capsules (IB-CP SRCs) were prepared by IB-SRPs and CP-IRPs packed together in capsules with the optimum doses of 200 and 13mg, respectively. The prepared pellets were evaluated by scanning electron microscopy and dissolution test. Pharmacokinetic studies in beagle dogs indicated that the optimized IB-CP SRCs had smaller individual differences and better reproducibility comparing with commercial available tablets. Additionally, IB-CP SRCs achieved consistency with in vivo and in vitro tests. Therefore, IB-CP SRCs could play a great role in rapid and long-term analgesic.