Study of controlled-release floating tablets of dipyridamole using the dry-coated method

Dipyridamole (DIP), having a short biological half-life, has a narrow absorption window and is primarily absorbed in the stomach. So, the purpose of this study was to prepare controlled-release floating (CRF) tablets of dipyridamole by the dry-coated method. The influence of agents with different viscosity, hydroxypropylmethylcellulose (HPMC) and polyvinylpyrollidon K30 (PVP K30) in the core tablet and low-viscosity HPMC and PVP K30 in the coating layer on drug release, were investigated. Then, a study with a three-factor, three-level orthogonal experimental design was used to optimize the formulation of the CRF tablets. After data processing, the optimized formulation was found to be: 80?mg HPMC K4M in the core tablet, 80?mg HPMC E15 in core tablet and 40?mg PVP K30 in the coating layer. Moreover, an in vitro buoyancy study showed that the optimized formulation had an excellent floating ability and could immediately float without a lag time and this lasted more than 12?h. Furthermore, an in vivo gamma scintigraphic study showed that the gastric residence time of the CRF tablet was about 8?h.     

A novel automated alternating current biosusceptometry method to characterization of controlled-release magnetic floating tablets of metronidazole

Context: Alternating Current Biosusceptometry is a magnetically method used to characterize drug delivery systems. This work presents a system composed by an automated ACB sensor to acquire magnetic images of floating tablets.

Objective: The purpose of this study was to use an automated Alternating Current Biosusceptometry (ACB) to characterize magnetic floating tablets for controlled drug delivery.

Materials and methods: Floating tablets were prepared with hydroxypropyl methylcellulose (HPMC) as hydrophilic gel material, sodium bicarbonate as gas-generating agent and ferrite as magnetic marker. ACB was used to characterize the floating lag time and the tablet hydration rate, by quantification of the magnetic images to magnetic area. Besides the buoyancy, the floating tablets were evaluated for weight uniformity, hardness, swelling and in vitro drug release.

Results: The optimized tablets were prepared with equal amounts of HPMC and ferrite, and began to float within 4?min, maintaining the flotation during more than 24?h. The data of all physical parameters lied within the pharmacopeial limits. Drug release at 24?h was about 40%.

Conclusions: The ACB results showed that this study provided a new approach for in vitro investigation of controlled-release dosage forms. Moreover, using automated ACB will also be possible to test these parameters in humans allowing to establish an in vitro.in vivo correlation (IVIVC).     

A formulation approach for development of HPMC-based sustained release tablets for tolterodine tartrate with a low release variation

Objective: The purpose of this study was to develop hydroxypropylmethylcellulose (HPMC)-based sustained release (SR) tablets for tolterodine tartrate with a low drug release variation.

Methods: The SR tablets were prepared by formulating a combination of different grades of HPMC as the gelling agents. The comparative dissolution study for the HPMC-based SR tablet as a test and Detrusitol^® SR capsule as a reference was carried out, and the bioequivalence study of the two products was also conducted in human volunteers.

Results: The amount of HPMC, the grade of HPMC and the combination ratio of different grades of HPMC had remarkable effects on drug release from the SR tablets. Both the test and reference products had no significant difference in terms of comparative dissolution patterns in four different media (f₂ > 50). Furthermore, the dissolution method and rotation speed showed no effects on the drug release from the two products. The 90% confidence intervals of the AUC_0–36 and C_max ratios for the test and reference products were within the acceptable bioequivalence intervals of log0.8–log1.25.

Conclusions: A HPMC-based SR tablet for tolterodine tartrate with a low release variation was successfully developed, which was bioequivalent to Detrusitol^® SR capsule.     

Influence of Hydroxypropyl Methylcellulose Mixture,Apparent Viscosity,and Tablet Hardness on Drug Release Using a 23 Full Factorial Design

ABSTRACT

This study investigates the effects of three factors: (1) use of a mixture of two different grades of hydroxypropyl methylcellulose (HPMC), (2) apparent viscosity, and (3) tablet hardness on drug release profiles of extended-release matrix tablets. The lot-to-lot apparent viscosity difference of HPMC K15M on in vitro dissolution was also investigated. Four test formulations were made, each containing 10% of a very water-soluble active pharmaceutical ingredient (API), 32% HPMC K15M, or a mixture of HPMC K100LV and HPMC K100M, 56% diluents, and 2% lubricants. Each formulation was made at two hardness levels. A 2³ full factorial design was used to study various combinations of the three factors using eight experiments conducted in a randomized order. Dissolution studies were performed in USP apparatus I. The values of t_50% (time in which 50% drug is released) and t_lag (lag time, the time taken by the matrix tablet edges to get hydrated and achieve a state of quasi-equilibrium before erosion and the advance of solvent front through the matrix occur) were calculated from each dissolution profile. The similarity factor (f₂) was also calculated for each dissolution profile against the target dissolution profile. A simple Higuchi-type equation was used to analyze the drug release profiles. Statistical analysis using analysis of variance (ANOVA) and similarity factor (f₂) values calculated from the data indicated no significant difference among the t_50% values and dissolution profiles respectively for all formulations. Within the 3.3–6 kp hardness range investigated, dissolution rates were found to be independent of tablet hardness for all the formulations. Although significantly shorter lag times were observed for the tablets formulated with low- and high-viscosity HPMC mixtures in comparison to those containing a single grade of HPMC, this change had no significant impact on the overall dissolution profiles indicated by the similarity factor f₂ values. From this study it can be concluded that lot-to-lot variability in apparent viscosity of HPMC should not be a concern in achieving similar dissolution profiles. Also, results indicated that within the viscosity range studied (12,000–19,500 cps) an HPMC mixture of two viscosity grades can be substituted for another HPMC grade if the apparent viscosity is comparable. Also, the drug release is diffusion-controlled and depends mostly on the viscosity of the gel layer formed.     

Optimization of piribedil mucoadhesive tablets for efficient therapy of Parkinson’s disease: physical characterization and ex vivo drug permeation through buccal mucosa

Objective: The aim of this study was optimization of buccal piribedil (PR) mucoadhesive tablets to improve its low bioavailability and provide controlled release for the treatment of Parkinson’s disease.

Methods: Buccal tablets were prepared by direct compression method using carbomer (CP), carboxymethyl cellulose (CMC), and hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Physical properties of powder mixtures and buccal tablets were evaluated. Physicochemical compatibility between ingredients was investigated with infrared spectroscopy and differential scanning calorimetry analysis. In vitro dissolution profiles and drug release kinetics of buccal tablets were investigated. Mucoadhesion and ex vivo permeation studies were performed using sheep buccal mucosa.

Results: Powder mixtures demonstrated sufficient flow properties and physical characteristics of all tablet formulations were within compendia limits. Tablet ingredients were absent of any chemical interactions. CP tablets displayed slower drug release compared to HPMC tablets with zero order release, while CMC tablets lost their integrity and released entire drug after 6?h following Higuchi model. All formulations displayed adequate mucoadhesion and steady state flux of PR through buccal mucosa were higher with HPMC compared to CP-containing tablets.

Conclusion: Overall, HPMC was found to combine desired controlled release and mucoadhesion characteristics with sufficient pharmaceutical quality for optimization of buccal tablets. Piribedil mucoadhesive buccal tablets designed for the first time may introduce a new alternative for the treatment of Parkinson’s disease.     

Evaluation of hydrophilic,hydrophobic and waxy matrix excipients for sustained release tablets of Venlafaxine hydrochloride

Objective: Venlafaxine is freely soluble In water and administered orally as hydrochloride salt In two to three divided doses. In the present investigation different release retarding matrices have been evaluated for sustained release of venlafaxine hydrochloride (VH) from the formulated tablets.

Materials and methods: Sustained release matrix tablets were formulated using different hydrophilic, hydrophobic and waxy materials as matrix formers. Tableting was done by pre-compression, direct compression and hot melt granulation depending on the type of matrix material used and evaluated for different tests. The formulated tablets were compared with commercial venlafaxine products. In vitro drug dissolution profiles were fitted In different mathematical models to elucidate the release mechanism.

Results: Dissolution data showed that commercial formulations Venlor XR^® and Venfax PR^® released the entire drug withIn 8?h where as the formulated tablets with hydroxypropylmethylcellulose (HPMC) and cetyl alcohol as matrix formers provided sustained release of drug for 14–15?h. The release was found to follow Hixson Crowel and Higuchi kinetics for HPMC and cetyl alcohol tablets, respectively.

Conclusion: The developed matrix tablet formulations with HPMC and cetyl alcohol provided sustained release profiles for prolonged periods than commercial formulations.     

Preparation and evaluation of floating tablets of pregabalin

Abstract

Floating tablets of pregabalin were prepared using different concentrations of the gums (xanthan gum and guar gum), Carbopol 974P NF and HPMC K100. Optimized formulations were studied for physical tests, floating time, swelling behavior, in vitro release studies and stability studies. In vitro drug release was higher for tablet batches containing guar and xanthan gum as compared to the batches containing Carbopol 974P NF. Tablet batches were subjected to stability studies and evaluated by different parameters (drug release, drug content, FTIR and DSC studies). The optimized tablet batch was selected for in vivo pharmacodynamic studies (PTZ induced seizures). The results obtained showed that the onset of jerks and clonus were delayed and extensor phase was abolished with time in treated groups. A significant difference (p?>?0.05) was observed in control and treated group behavior indicating an excellent activity of the formulation for a longer period (>12?h).     

The influence of HPMC concentration on release of theophylline or hydrocortisone from extended release mini-tablets

Context: Mini-tablets are compact dosage forms, typically 2–3 mm in diameter, which have potential advantages for paediatric drug delivery. Extended release (ER) oral dosage forms are intended to release drugs continuously at rates that are sufficiently controlled to provide periods of prolonged therapeutic action following each administration, and polymers such as hypromelllose (HPMC) are commonly used to produce ER hydrophilic matrices.

Objective: To develop ER mini-tablets of different sizes for paediatric delivery and to study the effects of HPMC concentration, tablet diameter and drug solubility on release rate.

Methods: The solubility of Hydrocortisone and theophylline was determined. Mini-tablets (2 and 3 mm) and tablets (4 and 7 mm) comprising theophylline or hydrocortisone and HPMC (METHOCEL? K15M) at different concentrations (30, 40, 50 and 60%w/w) were formulated. The effect of tablet size, HPMC concentration and drug solubility on release rate and tensile strength was studied.

Results and Discussion: Increasing the HPMC content and tablet diameter resulted in a significant decrease in drug release rate from ER mini-tablets. In addition, tablets and mini-tablets containing theophylline produced faster drug dissolution than those containing hydrocortisone, illustrating the influence of drug solubility on release from ER matrices. The results indicate that different drug release profiles and doses can be obtained by varying the polymer content and mini-tablet diameter, thus allowing dose flexibility to suit paediatric requirements.

Conclusion: This work has demonstrated the feasibility of producing ER mini-tablets to sustain drug release rate, thus allowing dose flexibility for paediatric patients. Drug release rate may be tailored by altering the mini-tablet size or the level of HPMC, without compromising tablet strength.     

Preparation and pharmacokinetics study on gastro-floating sustained-release tablets of troxipide

The purpose of this research aimed at preparing gastro-floating sustained-release tablets of troxipide and a further study on in vitro release and in vivo bioavailability. Under the circumstances of direct powder compression, the floating tablets were successfully prepared with HPMC as main matrix material, Carbopol as assistant matrix material, octadecanol as floating agent and sodium bicarbonate as foaming agent to float by gas-forming. The floating time and accumulative release amount as evaluation indexes were utilized to perform pre-experiment screening and single-factor test, respectively, while central composite design response surface method was applied for formulation optimization, followed by in vivo pharmacokinetic study in beagles after oral administration for floating tablets and commercial tablets used as the control. The results indicated that the floating sustained-release tablets held a better capability for floating and drug release and more satisfactory pharmacokinetic parameters, such as a lower C_max, a prolonged T_max, but an equivalent bioavailability calculated by AUC_0–24 compared to commercial tablets. So a conclusion was finally drawn that the floating sustained-release tablets possessing a good release property could be suitable for demands of design.     

Fabrication and in vitro evaluation of bidirectional release and stability studies of mucoadhesive donut-shaped captopril tablets

Objective: To obtain controlled release of captopril in the stomach, coated, mucoadhesive donut-shaped tablets were designed.

Materials and methods: Donut-shaped tablet were made of different ratios of diluents to polymer or combination of polymers by direct compression method. Top and bottom portions of the tablet were coated with water-insoluble polymer followed by mucoadhesive coating. Time of water penetration, measurement of tensile strength, mucoadhesion studies (static ex vivo and ex vivo wash-off) were taken into account for characterization of respective films. In vitro study has been performed at different dissolution mediums. Optimized batches were also prepared by wet granulation. Stability studies of optimized batches have been performed.

Results: The results of time of water penetration and tensile strength indicated positive response against water impermeation. Mucoadhesive studies showed that film thickness of 0.12?mm was good for retention of tablet at stomach. At pH 1.2, optimized batch of tablet made with hydroxypropyl methyl cellulose (HPMC) E15 as binder showed 80% w/w drug release within 4–5?h with maximum average release of 97.49% w/w. Similarly, maximum average releases of 96.36% w/w and 95.47% w/w were obtained with nearly same dissolution patterns using combination of HPMC E5 and HPMC E50 and sodium salt of carboxy methyl cellulose (NaCMC) 500–600 cPs instead of HPMC E15. The release profiles in the distilled water and pH 4.5 followed the above pattern except deviation at pH 6.8. Stability studies were not positive for all combinations.

Conclusion: Coated, mucoadhesive donut-shaped tablet is good for controlled release of drug in the stomach.     

Effect of polymer,plasticizer and filler on orally disintegrating film

Context: Difficulty in swallowing tablets or capsules has been identified as one of the contributing factors to non-compliance of geriatric patients. Although orally disintegrating tablet was designed for fast disintegration in mouth, the fear of taking solid tablets and the risk of choking for certain patient populations still exist.

Objective: The objective of this study was to develop and characterize orally disintegrating film (ODF), which was prepared using different combinations of polymers, plasticizers and fillers.

Materials and methods: Effects of hydroxypropyl methylcellulose (HPMC), polyethylene glycol 400 (PEG 400), glycerin, polyvinyl pyrrolidone (PVP), mannitol and microcrystalline cellulose (MCC) on physical property of ODF formed were studied. The ODF was prepared using the solvent casting method.

Results: Increase in HPMC concentration formed ODF with greater tensile strength. Incorporation of plasticizer (PEG 400 and glycerin) reduced tensile strength but increased elasticity of the ODF formed. PVP increased both tensile strength and elasticity of the ODF. Increase in MCC:mannitol ratio reduced the tensile strength and elasticity of the ODF. Disintegration time of film decreased corresponding to decrease in tensile strength of the film. Formulation R with the optimum tensile strength (13.10?N/mm²), bending flexibility (40 times) and disintegration time (41.50?s) was chosen as final formulation. A total of 80% of the drug was released within five minutes and the ODF was stable at least for one year actual condition.

Conclusion: An ODF containing donepezil HCl was developed and characterized. The donepezil HCl ODF has the potential to improve the compliance of Alzheimer disease patients.     

Vitamin B12 buccoadhesive tablets: auspicious non-invasive substitute for intra muscular injection: formulation,in vitro and in vivo appraisal

Attempting to prepare a convenient bioavailable formulation of vitamin B₁₂ (cyanocobalamin), 17 tablet formulations were prepared by direct compression. Different concentrations of hydroxypropyl methyl cellulose (HPMC), carbopol 971p (CP971p), and chitosan (Cs) were used. The tablets were characterized for thickness, weight, drug content, hardness, friability, surface pH, in vitro drug release, and mucoadhesion. Kinetic analysis of the release data was conducted. Vitamin B₁₂ bioavailability from the optimized formulations was studied on rabbits by the aid of enzyme-linked immunosorbent assay. Neurotone^® I.M. injection was used for comparison. HPMC (F1-F4), CP971p (F5-F8), and HPMC/CP971p (F12-F15)-based formulations showed acceptable mechanical properties. The formulated tablets showed maximum swelling indices of 232?±?0.13. The surface pH values ranged from 5.3?±?0.03 to 6.6?±?0.02. Bioadhesive force ranged from 66?±?0.6 to 150?±?0.5?mN. Results showed that CP971p-based tablets had superior in vitro drug release, mechanical, and mucoadhesive properties. In vitro release date of selected formulations were fitted well to Peppas model. HPMC/CP971p-based formulations showed bioavailability up to 2.7-folds that of Neurotone^® I.M. injection.     

Optimization and characterization of gastroretentive floating drug delivery system using Box-Behnken design

Context: One among many strategies to prolong gastric residence time and improve local effect of the metronidazole in stomach to eradicate Helicobacter pylori in the treatment of peptic ulcer was floating drug delivery system particularly effervescent gastroretentive tablets.

Objective: The objective of this study was to prepare and evaluate, effervescent floating drug delivery system of a model drug, metronidazole.

Methods: Effervescent floating drug delivery tablets were prepared by wet granulation method. A three-factor, three levels Box-Behnken design was adopted for the optimization. The selected independent variables were amount of hydroxypropyl methylcellulose K 15M (X₁), sodium carboxy methylcellulose (X₂) and NaHCO₃ (X₃). The dependent variables were floating lag time (Y_FLT), cumulative percentage of metronidazole released at 6th h (Y₆) and cumulative percentage of metronidazole released at 12th h (Y₁₂). Physical properties, drug content, in vitro floating lag time, total floating time and drug release behavior were assessed.

Results: Y_FLT range was found to be from 1.02 to 12.07?min. The ranges of other responses, Y₆ and Y₁₂ were 25.72?±?2.85 to 77.14?±?3.42 % and 65.47?±?1.25 to 99.65?±?2.28 %, respectively. Stability studies revealed that no significant change in in vitro floating lag time, total floating time and drug release behavior before and after storage.

Conclusion: It can be concluded that a combination of hydroxypropyl methylcellulose K 15M, sodium carboxy methylcellulose and NaHCO₃ can be used to increase the gastric residence time of the dosage form to improve local effect of metronidazole.     

Design and optimization of gastric floating sustained-release mini-tablets of alfuzosin hydrochloride based on a factorial design: in vitro/in vivo evaluation

Abstract

The purpose of this research was to develop multiple-unit gastric floating mini-tablets and to evaluate the possibility of using these mini-tablets as a delivery system to improve the drug absorption for drugs with a narrow absorption window. Mini-tablets were prepared using hydroxypropyl methylcellulose (HPMC K100M) and carbopol 971P as release retarding agents and sodium bicarbonate (NaHCO₃) as gas-forming agent. The properties of the prepared mini-tablets in terms of floating characteristic parameters and in vitro release were evaluated. Furthermore, in vivo gastric retention study in rats and in vivo pharmacokinetic study in rabbits of the optimized formulation were performed. The optimized mini-tablets containing 45% HPMC K100M, 15% stearyl alcohol, 13% carbopol 971P, and 12% NaHCO₃ were found to float immediately within 1?min and duration more than 9?h. The in vivo gastric retention study results indicated that the mini-tablets could retain in the stomach for more than 6.67?h. Furthermore, the AUC_0?t of the floating mini-tablets (6849.83?±?753.80?h ng·mL^?1) was significantly higher than that of marketed sustained-release tablets XATRAL®XL (4970.16?±?924.60?h ng·mL^?1). All these results illustrated that the gastric floating mini-tablets might be a promising drug delivery system for drugs with a narrow absorption window.     

In vitro and in vivo evaluation of hydrophilic and hydrophobic polymers-based nicorandil-loaded peroral tablet compared with its once-daily commercial sustained-release tablet

Context: Hydrophilic and hydrophobic polymer-based nicorandil (10 mg)-loaded peroral tablets were prepared using the wet granulation technique. The influence of varying amounts of hydroxypropyl methylcellulose (HPMC) (30–50 mg), ethylcellulose (2–4 mg), microcrystalline cellulose (5–20 mg) and Aerosil^® (5–12 mg) in conjunction with the constant amounts (3 mg) of glidant and lubricant (magnesium stearate and talc) on the in vitro performances of the tablets (hardness, friability, weight variation, thickness uniformity, drug content, and drug release behavior) were investigated. Objective: The objectives of this study were (i) to select a nicorandil-loaded peroral tablet that matched the in vitro dissolution profile of once-daily commercial sustained-release tablet, and (ii) to compare the in vivo sustaining/controlling efficacy of the selected peroral tablet with that of its commercial counterparts. Results and Discussion: Because the nicorandil (10 mg)-loaded tablet prepared based on F-IX composition (50 mg HPMC, 4 mg ethylcellulose, 10 mg MCC and 3 mg glidant and lubricant) showed a release profile comparable to that of the Nikoran^® OD SR tablet release profile, the tablet with this composition was considered to be the optimized/selected formulation and, therefore, was subjected to stability study and in vivo study in rabbits. Despite of the higher C_max and AUC values obtained with the optimized tablet, there was no sign of difference between the optimized- and Nikoran^® OD SR- tablets following a single-dose crossover oral administration into rabbit. Conclusion: The optimized tablet could be used as an alternative to the commercial once-daily tablet.     

In Vitro and In Vivo Adhesion Testing of Mucoadhesive Drug Delivery Systems

Bioadhesive tablets were prepared by physical mixing of polymers and drug, then granulating and compressing into a tablet. The mucoadhesion was evaluated by shear stress measurement, detachment force measurement, and X-ray photography of the rabbit gastrointestinal tract. The strong interaction between the polymer and the mucous lining of the tissue helps increase contact time and permit localization. Polymers like hydroxypropyl methylcellulose K4M (HPMC K4M), hydroxypropyl methylcellulose 100 cps (HPMC 100 cps), carbopol-934, sodium carboxy methylcellulose (Na CMC), guar gum, and polyvinylpyrrolidone (PVP) were tested by shear stress measurement and detachment force measurement methods. HPMC K4M, showing maximum bioadhesion, was used in further studies. Adhesion was maximum between pH 5 and pH 6. Maximum adhesion was observed in the duodenum, followed by the jejunum and ileum. Barium sulfate (BaSO₄) matrix tablets containing polymer and drug were subjected to X-ray studies in rabbits, and it was found that the tablet was mucoadhesive even after 8 hr. Enteric coating did not show any effect on mucoadhesion after passing from the stomach.     

Evaluation of performance of co crystals of mefloquine hydrochloride in tablet dosage form

Objective: The objective of present investigation was to evaluate performance of cocrystals of Mefloquine Hydrochloride (MFL) in tablet dosage form. Our previous investigation showed significant effect of cocrystal formers on improving the solubility and dissolution rate of Mefloquine hydrochloride by cocrystallization method when prepared by solution cocrystallization method.

Materials and methods: Prepared cocrystals of MFL with different ratio of cocrystal formers were incorporated in tablet dosage form and evaluated for micrometric properties, drug content, hardness, disintegration test, vitro dissolution studies and stability studies. Performance was compared with laboratory prepared tablet of MFL 250 mg.

Results: The considerable improvement in the dissolution rate was observed in case of cocrystals based tablets than pure MFL tablets.

Discussion and conclusion: So we can incorporate cocrystals in tablet dosage form to enhance in vitro and in vivo performance. To the best of our knowledge, this is the first report, cocrystals has been evaluated in tablet dosage form.     

Determination of precipitation inhibitory potential of polymers from amorphous solid dispersions

Abstract

Precipitation inhibitory potential of polymers screened from precipitation study may be altered once it is formulated in amorphous solid dispersions (ASDs).

Objective: Present study was embarked with an objective to determine whether the polymers retain the same inhibitory potential after formulating them into ASDs.

Methods: Screening of polymers was based on a new dimensionless parameter ‘Supersaturation Holding Capacity (SHC)’ calculated from the precipitation study. Nifedipine ASDs were formulated using HPMC E3 and HPMC E50 (high SHC values), and HPMC K100M, PVP K25, and HPC M (low to moderate SHC values). Generated ASDs were characterized by DSC, FTIR, and PXRD and evaluated for stability under accelerated conditions (40?C and 75% RH) for 6 months.

Results: Thermal analysis of the ASDs and theoretical prediction of the glass transition temperature (T_g) suggested a linear dependency of T_g on the content of HPMC E3 and HPMC E50. Under accelerated stability conditions, all ASDs of nifedipine with HPMC E3 and HPMC E50 (except ASDs with 70% drug load) were stable, which could be attributed to the molecular level dispersion of the drug in these polymers. SHC parameter calculated from the apparent solubility profile gave following rank order HPMC E50 (3.4)?>?HPMC E3 (3.2)?>?HPMC K100M (1.29)?>?PVP K25 (1.09)?>?HPC M (0.99). SHC calculated from the apparent solubility profile of ASDs demonstrated good agreement between the solution state and solid state screening of the polymers for precipitation inhibition. During dissolution study, nearly four-fold enhancement has been observed with ASDs comprising HPMC E3 and HPMC E50.

Conclusions: The outcome of the study concluded that SHC can be a promising parameter in the screening of polymers for the development of the ASDs.     

Development of sustained release gastro-retentive tablet formulation of nicardipine hydrochloride using quality by design (QbD) approach

The objective of the present study was to develop a sustained release gastro-retentive (SRGR) tablet formulation of nicardipine hydrochloride (HCl) for once-a-day dosing using the quality by design (QbD) approach. The quality target product profile of nicardipine HCl SRGR tablet formulation was defined, and critical quality attributes (CQAs) were identified. Potential risk factors were identified using a fish bone diagram and failure mode effect analysis (FMEA) tool and screened by the Plackett–Burman design, and finally nicardipine HCl SRGR tablet formulation was optimized using the Box–Behnken design. The tablets were prepared by a direct compression technique using polymers such as hydroxypropylmethylcellulose (HPMC K15M), glyceryl behenate, alone or in combinations and other standard excipients. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of polymers and sodium bicarbonate on the drug release profile and floating properties were investigated as these parameters are likely to affect the desired once-a-day dosing regimen and finally the therapeutic efficacy of SRGR drug delivery systems. It was observed that formulation variables X₁: Glyceryl behenate (mg/tab) and X₂: HPMC K15M (mg/tab) strikingly influenced the drug release (%) (Y₁), whereas floating lag time (min) (Y₂) was significantly impacted by the formulation variable X₃: Sodium bicarbonate (mg/tab). A design space plot within which the CQAs remained unchanged was established at a lab scale. In conclusion, this study demonstrated the suitability of a glyceryl behenate-HPMC K15M polymer combination along with sodium bicarbonate to achieve SRGR tablet formulation for once-a-day dosing of nicardipine HCl using the systematic QbD approach.     

In vitro release of ketoprofen from hydrophilic matrix tablets containing cellulose polymer mixtures

The effect of cellulose ether polymer mixtures, containing both hydroxypropylcellulose (HPC) and hydroxypropylmethylcellulose (HPMC K15M or K100M), on ketoprofen (KTP) release from matrix tablets was investigated. In order to evaluate the compatibility between the matrix components, Raman spectroscopy, scanning electron microscopy (SEM), and X-ray powder diffraction (XRPD) experiments were performed. The results evidence the absence of significant intermolecular interactions that could eventually lead to an incompatibility between the drug and the different excipients. Formulations containing mixtures of polymers with both low and high viscosity grades were prepared by a direct compression method, by varying the polymer/polymer (w/w) ratio while keeping the drug amount incorporated in the solid dispersion constant (200?mg). The hardness values of different matrices were found within the range 113.8 to 154.9 N. HPLC analysis showed a drug content recovery between 99.3 and 102.1%, indicating that no KTP degradation occurred during the preparation process. All formulations attained a high hydration degree after the first hour, which is essential to allow the gel layer formation prior to tablet dissolution. Independent-model dissolution parameters such as t_10% and t_50% dissolution times, dissolution efficiency (DE), mean dissolution time (MDT), and area under curve (AUC) were calculated for all formulations. Zero-order, first-order, Higuchi, and Korsmeyer–Peppas kinetic models were employed to interpret the dissolution profiles: a predominantly Fickian diffusion release mechanism was obtained – with Korsmeyer–Peppas exponent values ranging from 0.216 to 0.555. The incorporation of HPC was thus found to play an essential role as a release modifier from HPMC containing tablets.