HPMC E5 Research Articles

Formulation and Evaluation of Sustained Release Pellets of Verapamil HCL

Verapamil Hydrochloride, an antihypertensive agent which is used as a calcium channel blocker. The aim of the present study was to formulate and evaluate Verapamil HCL sustained release pellets. The work is to obtain Verapamil HCL sustained release pellets by using HPMC based polymers i.e., HPMC AN6, HPMC E5, HPMC E15 in the sustained release layer. The verapamil Hydrochloride has pH-dependent solubility. To overcome the pH dependent solubility Fumaric acid was used that which provides micro-acidic environment. Different Ratios of Ethyl-cellulose and HPMC polymers were used to optimise and evaluate the formulation for the sustained release of the drug. It uses the Pelletization technology. This technique is practised to produce pellets of uniform size with high drug loading capacity and also to prevent the segregation and dust.

Formulation and Evaluation of Simvastatin Transdermal Drug Delivery System

Transdermal patches are a cutting-edge drug delivery technology that is essential in the management of many disorders. As first-pass metabolism is avoided, TDDS can effectively increase bioavailability and aid in the delivery of drug molecules into the systemic circulation at a planned and controlled rate. This study's goal was to create matrix-type simvastatin transdermal patches utilising the solvent evaporation method and various polymer ratios, including HPMC 15 cps, HPMC E5, and Eudragit S 100. Plasticizers like glycerine, propylene glycol, and PEG 200 are utilised, along with solvents like methanol and chloroform. According to FTIR studies, pure drugs and excipients are compatible with each other. The tested patches are assessed for thickness, weight variation, folding endurance, moisture content, drug content, surface pH, and in vitro diffusion studies. The results indicated that the formulation F5 showed better characteristic properties and in vitro drug diffusion.

Development, Characterization and In vivo Pharmacokinetic Studies of Olmesartan Medoxomil Nanosuspension for the Effective Treatment of Hypertension

Introduction: The present work aims to increase the saturation solubility and the bioavailability of Olmesartan medoxomil (OM) via an acid-base neutralization-based nanosuspension technique. Method: The initial screening studies revealed that changes in the concentration of HPMC E15 (100-200 mg), mechanical stirring speed (SS) (900-1200 rpm) and stirring time (ST) (60-120 min) affected the responses. Effects produced by the factors (HPMC E15, SS, and ST) on responses (particle size, PDI, and cumulative % drug release (%CDR)) were investigated using a 2!!! !!!fractional factorial design with replicates and four midpoints. For the development of Olmesartan medoxomil nanosuspension, an acid-base neutralization technique was employed. Result: Pareto chart, perturbation plots and ANOVA were used to identify significant factors. The p-value <0.05 indicated the factors to be considered significant. The Particle size and PDI of all formulations ranged from 286.7 nm - 718.1 nm and 0.146 – 0.415, respectively. Drug release from all formulations ranged from74.0-103.7%. Pure drug solubility and optimized formula solubility were reported to be 108.6 g/ml and 1650.72 g/ml, respectively. Contour and 3D surface plots led to the identification of design space in which HPMC E15, SS and ST can be oriented at 148.8-151 mg, 959-1000 rpm and 106-120 min, respectively, to get particle size <500 nm, PDI <0.5 and % CDR >95%.SEM results indicated that the particles were nearly spherical. Conclusion: In vivo pharmacokinetic studies conducted in Wistar rats exhibited ∼4.7 folds enhancement in optimized OM nanosuspension oral bioavailability compared to pure drug. It can be concluded that the selected method and application of the design of the experimentation technique enhanced the saturation solubility and bioavailability of OM.

Evaluation and Pharmacokinetic Study in healthy human volunteers of developed bilayer thin films containing Piroxicam and Zolmitriptan

In the current work, sublingual bilayer thin films (SBTFs) containing piroxicam and zolmitriptan, were prepared by solvent casting technique using HPMC E15, pullulan afterwards evaluated for their physicomechanical properties, disintegration time and in-vitro drug release. A single dose of formulated SBTFs containing piroxicam (10mg) and Zolmitriptan (2.5mg) was administered to healthy volunteers and their blood samples were withdrawn at predefined time interval for in-vivo pharmacokinetic studies. Plasma concentration of drugs were analysed using a validated HPLC-MS/MS method. The pharmacokinetic parameters were obtained and compared with pharmacokinetic data of marketed formulation. The thickness, weight variation, folding endurance and pH of the films was found to be within the acceptable range. The in-vitro disintegration time varied from 27-45 sec and drug content was found to be 96.01- 100.62% for all the formulation. Formulation B3 showed drug release of 92% within 3-4.5 mins. The plasma concentration time curve helped in assessing the pharmacokinetic parameters i.e. AUC0-24, t1/2, Cmax, tmax, and Vd. The plasma concentration time profile of both drugs indicated the increase of AUC, bioavailability, elimination half-life and Vd when compared with the pharmacokinetic parameters of marketed formulation which helped in the rapid onset of action in the management of acute pain. The results suggested that plasma drug concentration of active ingredient started appearing in a significant amount within 30 minutes which indicated that the developed sublingual delivery system had effectively delivered the drug into the systemic circulation.

ENCAPSULATION OF EXEMESTANE WITH β-CYCLODEXTRIN AND TERNARY AGENT: FORMULATION, EVALUATION AND ANTICANCER ACTIVITY

Objective: A potent aromatase inhibitor, Exemestane, is well known for its anticancer action in breast neoplasm. The vital problem of this medicament is its poor aqueous solubility, which hinders its dissolution in body fluids. Therefore, the present study targets to enhance the water solubility of Exemestane by means of its complexation with β-cyclodextrin and a suitable ternary agent. Methods: Inclusion complexes of Exemestane with β-cyclodextrin and ternary agent were prepared by kneading and lyophilization technique. Different hydrophilic polymers and organic acids were screened for their influential ability as a co-complex with a carrier; β-cyclodextrin. The validation of complex formation was carried out by various solid-state techniques. The geometry of Exemestane in the β-cyclodextrin cavity was picturized in docking studies. The in vitro anticancer activity of prepared inclusion complex formulations carried out using MCF-7 cell lines Results: Phase solubility analysis proved HPMC E5 as the best ternary agent for complexation of Exemestane with β-cyclodextrin as it improved the stability constant of the drug from 665.92 M-1 to 1238.38 M-1. The synthesized binary and ternary inclusion complexes exhibited 2.74 and 4.62 times enhanced solubilization of Exemestane. Likewise, the dissolution characteristics of Exemestane were improved, and drug release was increased by 1.18 and 1.42 times with binary and ternary freeze-dried formulations. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) study results presented the formation of binary and ternary complexes with significantly drooped crystallinity. Docking studies predicted encapsulation of rings A, B, and C of Exemestane in the cavity of β-cyclodextrin. In-line results were obtained in Fourier transform infrared (FTIR) studies. The cell growth inhibition of 62.78 % was achieved with a ternary complex of Exemestane which was far superior than the pure active moiety that showed mere 44.56 % of inhibition. Conclusion: Altogether, it can be concluded that the inclusion complex of Exemestane boosted its aqueous solubility, resulting in its increased dissolution and in vitro anticancer activity in a breast cancer MCF-7 cell line.

Formulation, Evaluation and Comparison of Mesalamine compression coated tablets by using Natural and Semi synthetic polymers

The main objective of this research paper is to formulate, evaluate and compare compression-coated tablets of Mesalamine using natural and synthetic polymer. The natural polymers used were pectin and Xanthan gum and the synthetic polymer used was HPMC E50 LV. Initially tablets were prepared by direct compression method using different polymers and both pre-compression and post-compression evaluation was conducted. Using the same polymers compression coated tablets of mesalamine were prepared by compression coating method using Cellulose acetate phthalate as the enteric polymer. These tablets were also subjected to pre-compression and post-compression evaluation and all the values obtained were in acceptable limits. Dissolution studies were conducted in different media having pH 1.2, 6.8 and 7.4. The dissolution results showed the drug release of uncoated tablet of HPMC E50 LV was 108.42% at 480 minutes, Pectin was 100.53% at 300 minutes and Xanthan gum was 108.73% at 90 minutes. The drug release of coated tablets of HPMC E50 LV was 100.42% at 680 minutes, Pectin was 102.31% at 580 minutes and Xanthan gum was 100.42% at 300 minutes. Hence the study showed that the compression coated tablets of mesalamine using HPMC E50 LV showed delayed release of the drug in 680 minutes.
 Keywords: Mesalamine, Colon targeting drug delivery system, Compression coating method, Delayed release, Cellulose acetate phthalate.

FORMULATION AND CHARACTERIZATION OF AMLODIPINE LOADED IN-SITU FILM FORMING HYDROGEN FOR DERMAL DRUG DELIVERY

Present work involves the development of novel in situ film-forming hydrogels (FFH) consisting of primarily Carbopol 934P, HPMC E50 LV and PEG 400. Here, propylene glycol was employed as a permeation enhancer for studying its effect in the formation of FFH and drug permeation. Prepared formulations were assessed for various parameters. Prepared FFH was uniform in weight and thickness with acceptable pH, viscosity and spreadability. Prepared FFH was able to form the in- situ film on the skin surface within 7min. propylene glycol was found to have a direct relationship with moisture content, moisture uptake and water vapour transmission. Higher drug encapsulation and better permeation were also observed when the concentration of propylene glycol was increased. All formulations were non-irritating to the skin and thus acceptable. In conclusion, prepared in-situ film-forming hydrogel can be effectively used as a novel dermal drug delivery system.

Cellulose Derivative-Based Bioadhesive Blend Patch for Transdermal Drug Delivery

In this study, matrix-type transdermal patches of glibenclamide were developed using a combination of hydrophilic and hydrophobic polymers for investigating the efficacy of transdermal carriers. A cellulose derivative, HPMC E50, was used as a hydrophilic matrix-forming polymer, and Eudragit RS 100 was used as a hydrophobic polymer. The solvent casting technique was employed to develop a transdermal blend patch formulation using chloroform and methanol as the casting solvent. No drug–polymer interaction was observed by the FTIR study. The membrane permeation study exhibited a sustained release of glibenclamide up to 12 h within a range of 76.15 ± 2.80% to 101.01 ± 0.33% depending on the polymeric ratio. The increased concentration of Eudragit RS 100 in different formulations has gradually decreased the amount of drug penetration through the membrane. The kinetic analysis showed the release is best explained by zero-order kinetics, followed by Higuchi and first order. The release exponent suggested shifting of non-Fickian diffusion to the super case II transport drug release mechanism when Eudragit RS 100 concentration was increased. It is concluded that the developed formulations may be a better alternative to the conventional oral delivery of glibenclamide.

FORMULATION AND EVALUATION OF FLOATING MICROSPHERES OF LANSOPRAZOLE

Lansoprazole has a short half-life and it gets absorbed only in the proximal part of the small intestine. Floating microspheres of such a drug floats on the stomach contents and releases the drug slowly for longer periods of time. Thus, to overcome the problem like short half-life and to enhance the absorption and bioavailability, floating microspheres of lansoprazole were formulated by spray drying method using ethyl cellulose and HPMC E15 as polymers and dichloromethane and ethanol as solvents. Prepared microspheres were evaluated for micrometric properties, percentage yield, drug content, buoyancy percentage, differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). All designed formulations showed in vitro buoyancy between 72 to 92 %. In vitro dissolution study showed cumulative drug release between 84 to 97 % within 8 h. SEM study showed that formulated microspheres were porous and spherical with rough surface.

Incorporation of itraconazole nano-co-crystals into multiparticulate oral dosage forms

Limited research has been performed on the downstream processing of nano-co-crystal suspensions into solid oral dosage forms. The objectives of this study were to evaluate the impact of three downstream processes (wet granulation, spray granulation and bead layering) on the performance of itraconazole-succinic acid (ITZ-SUC) nano-co-crystal suspension. An optimized ITZ-SUC nano-co-crystal suspension mixed with HPMC E5 was utilized for the downstream processing. The suspension was converted in the solid state either by wet or spray granulation (with microcrystalline cellulose or lactose as substrates) or by layering onto microcrystalline cellulose and sugar beads. The multiparticulate solid dosage forms were characterized by optical microscopy, differential scanning calorimeter (DSC), X-ray powder diffraction (XRPD) and in situ dissolution studies. Spray granulation and bead layering resulted in less particle aggregation, a faster dissolution rate, and higher kinetic solubility when compared to wet granulation. ITZ-SUC nano-co-crystals spray granulated with lactose resulted in higher kinetic solubility profiles compared to microcrystalline cellulose granules. The type of bead core had no impact on the dissolution behavior. A slower dissolution and decreased kinetic solubility were observed with increasing drug loading for sprayed granules when microcrystalline cellulose was used as substrate. All dosage forms were stable under accelerated storage conditions (40 °C/75% RH) when blistered. Nano-co-crystals incorporated in granules were less stable than layered beads under non-blistered condition. Nano-co-crystals layered sugar beads are an interesting alternative to amorphous solid dispersion; a comparable kinetic solubility but a faster drug release were achieved. This study identified bead layering as a superior downstream process approach for incorporating ITZ-SUC nano-co-crystals into an oral solid dosage form without compromising drug dissolution.

Osmolality of Excipients for Parenteral Formulation Measured by Freezing Point Depression and Vapor Pressure - A Comparative Analysis.

To investigate the difference in methods to determine the osmolality in solutions of stabilizers used for long-acting injectable suspensions. The osmolality was measured by freezing point depression and vapor pressure for 11 different polymers and surfactants (PEG 3350, 4000, 6000, 8000, 20,000, PVP K12, K17 and K30, poloxamer 188, 388 and 407, HPMC E5, Na-CMC, polysorbate 20 and 80, vitamin E-TPGS, phospholipid, DOSS and SDS) in different concentrations. Independently of the measuring method, an increase in osmolality with increasing concentration was observed for all polymers and surfactants, as would be expected due to the physicochemical origin of the osmolality. No correlation was found between the molecular weight of the polymers and the measured osmolality. The osmolality values were different for PVPs, PEGs, and Na-CMC using the two different measurement methods. The values obtained by the freezing point depression method tended to be similar or higher than the ones provided by vapor pressure, overall showing a significant difference in the osmolality measured by the two investigated methods. For lower osmolality values (e.g. surfactants), the choice of the measuring method was not critical, both the freezing point depression and vapor pressure could be used. However, when the formulations contained higher concentrations of excipients and/or thermosensitive excipients, the data suggests that the vapor pressure method would be more suited.

Formulation and Evaluation of Fast Disintegrating Tablets Containing Sertraline Solid Dispersion Using Plantago Ovata

The aim of the present research is to formulate Sertraline Hydochloride solid dispersion (SRT-SD) fast disintegrating tablets. The speed of onset of action of antidepressant drug is clinically important for several reasons. Fast disintegrating tablets of SRT-SD was formulated by using natural superdisintegrant adopting direct compression method to minimize time of onset of action and also become economic. The study describes formulation of solid dispersion of SRT using HPMC E5 as a carrier and further converting SRT-SD into fast disintegrating tablets utilizing Plantago ovata mucilage as natural superdisintegrant. All tablets formulations were evaluated for various pre and post compression parameters. The F1 batch showed release kinetics closest to Serta® with maximum r2 (0.9991) value was considered to be the optimized batch and showed hardness of 3.10 kg/cm2, disintegration time of 28.00 second and dissolution of 95 % in 12 min. The stability study clearly indicate that optimized batch can increase the disintegrating and dissolution time of SRT and utilized as prominent alternative for the treatment of depression.

Development, optimization and characterization of hydrocolloid based mouth dissolving film of Telmisartan for the treatment of hypertension

Telmisartan, a BCS class II antihypertensive, has low oral bioavailability due to first-pass metabolism and a poor solubility profile, causing dissolving problems. Telmisartan is a suitable choice for the Rapid Release Drug Delivery System since it needs rapid absorption for a quick beginning of the activity. The goal of this research was to create and describe a solid dispersion employing hydrocolloid incorporated mouth dissolving film of Telmisartan. To make a Mouth Dissolving Film, first, prepare a solid dispersion using the Kneading Method, then use the Solvent Casting Metrpose of screening Carrier for the further formulation, solid dispersion is assessed for solubility, drug content, and drug release rate. The in-vitro drug release investigation revealed that solid dispersion had better solubility and rapid drug release than pure drug. Physical appearance, surface PH, thickness uniformity, disintegration duration, drug content uniformity, folding durability, and in-vitro drug release were among the physicochemical and mechanical parameters assessed on the produced films. A 32-level factorial design was used to improve the approach. The effects of film appearance, disintegrating time, and in-vitro drug release behavior on the composition of Film-forming polymer(hydrocolloids) and Super disintegration were investigated. The in-vitro drug release and disintegration time of the optimized batch were found to be 91.83 percent and 29 sec, respectively. These positive conclusions demonstrated that mouth dissolving film of Telmisartan can be formulated using HPMC E15 as a film-forming polymer and Sodium Starch Glycolate as a super disintegrant for improving bioavailability and therapeutic outcome.

EFFECT OF HYDROPHILIC POLYMER ON DESIGN EXPERT ASSISTED ORO-DISPERSIBLE STRIP (ODS) OF ISOSORBIDE MONONITRATE

Oral conventional formulations like tablets, capsules and liquids have many limitations. Due to this and patient incompliance, there is a need to develop new formulations with better efficiency and stability. The aim of the present study was to develop and optimize fast dissolving Oro-dispersible strips (ODS) of isosorbide mononitrate by 32 -full factorial design. HPMC E15 (X1 ) concentration and glycerin (X2 ) concentration were selected as the independent variables, whereas, in vitro disintegration time (Y1 ), percent drug release (Y2 ) and tensile strength (Y3 ) were selected as dependent variables. Fast dissolving Oro-dispersible strips of isosorbide mononitrate were prepared by the solvent casting method.Tensile strength, disintegration time and in vitro dissolution of ODS of the strip were found to be within accepted range for optimized formulation. Statistical validity of the polynomials was established by ANOVA using Design-Expert software. The study suggests isosorbide mononitrate fast dissolving Oro-dispersible strip as potential alternative dosage form in management of angina pectoris.

Supersaturable self-emulsifying drug delivery system: A strategy for improving the loading and oral bioavailability of quercetin

Supersaturable Lipid based drug delivery systems have gained much attention as bio-enabling formulation approach for oral delivery of drugs with high dose. Hence, the present investigation involves the preparation of quercetin (QT) loaded supersaturable self-emulsifying drug delivery system (QT-sSEDDS). Capmul® MCM EP, Tween® 20 and ethanol were used as chief components of preconcentrate which were selected based on solubility studies. Precipitation inhibitors (PI) were screened based on apparent drug concentration profile with respect to time where, HPMC E5 at 2.5% w/w was found suitable for the desired purpose. The QT-sSEDDS were characterised for their size, stability, functional stability and precipitate characterization, which revealed promising results. Further, solubilisation potential of QT-sSEDDS was evaluated using pH-stat lipolysis method which revealed ∼1.25 fold higher %QT content in aqueous state in comparison to QT-sSEDDS without PI. The cell uptake studies on Caco-2 cells (qualitative and quantitative) revealed significantly higher uptake in case of sSEDDS (Coumarin-6 or QT loaded) over free groups. These in vitro results were corroborated by in vivo pharmacokinetic data where, QT-sSEDDS revealed ∼2.2 and 2-fold increase in Cmax (at 4 h) and AUC respectively in comparison to conventional QT-SEDDS. Hence, it can be suggested that sSEDDS can potentially be used in delivering poorly soluble drug, QT which shows dose dependent bioavailability.

Press-Coated Aceclofenac Tablets for Pulsatile Drug Delivery: Formulation and In Vitro Evaluations.

The symptoms of some diseases show circadian rhythms, such as the morning stiffness associated with pain at the time of awakening in rheumatoid arthritis. Therapy for such diseases doesn’t require immediate release or sustained release of medicament. In such therapies, pulsatile drug release is more suitable with a programmed drug release. The purpose of this research was to formulate press-coated aceclofenac tablets for pulsatile drug delivery with a distinct delay time of no drug release and release of the drug when it is more likely desired (i.e., after 5 to 6 h). Immediate release core tablets having aceclofenac were formulated. Three formulations, F1, F2, and F3, were prepared with variable concentrations of sodium croscarmellose. Pre- and post-compression tests were performed on the core tablets. The selection criteria included the lowest disintegration time as a requirement of pulsatile drug delivery with an immediate release core and a delayed release coat. The disintegration times of F1, F2, and F3 were 120 s, 60 s, and 15 s, respectively. Therefore, the F3 formulation was selected as the core tablet formulation because it had the shortest disintegration time (15 s). The core tablets were press-coated using different polymers, such as HPMC K100M, Eudragit L100, HEC, and HPMC E5. The polymers were used in the coatings to hinder the release of the core for the desired time. 36 formulations of polymer were prepared: A1 to A10 had HPMC K100M and Avicel PH102; formulations B1 to B6 had HPMC K100M, Eudragit L100, and Avicel PH102; formulations C1 to C7 had HPMC K100M and hydroxyethyl cellulose; formulations D1 to D7 had HPMC K100M and HPMC E5; and formulations E1 to E6 had changed the coating weight of the formulation used for D6 (having HPMC K100M and HPMC E5 in the ratio of 12.5% to 87.5%). Evaluations of the press-coated tablets were carried out through thickness, hardness, weight variation, friability, and in vitro dissolution tests. These parameters concluded that the formulation of E6, having HPMC K100M and HPMC E5 in the ratio of 12.5% to 87.5% at 600 mg weight, was the most optimum formulation as it showed 3.5% drug release after 4 h, 21.4% drug release after 5 h, and 99.27% drug release after 6 h.

Orodispersible films of Ledipasvir and Sofosbuvir Combination: Formulation optimization and development using Design of Experiments

Ledipasvir (LDV) and sofosbuvir (SBV) are poorly soluble drugs and hence dissolution limited bioavailability is a major concern. Further, the high total dose of this combination (LDV-90mg and SBV-400mg) may cause swallowing difficulties if formulated into tablets. Considering these challenges, it was aimed in the current research work to develop orodispersible films (ODFs) for this combination to enhance dissolution thereby bioavailability and also patient convenience. ODFs, because of their ready dispersibility in the oral cavity dissolution would be rapid and also high doses of drugs can be incorporated avoiding swallowing difficulties. HPMC E15 was taken as the film former. Thickness of the films (50µm – 150µm), concentration of superdisintegrant (sodium starch glycolate 6-12% w/w) and concentration of plasticizer (polyethylene glycol 400, 10-20% w/w) were taken as three formulation factors each at three levels. Using Design Expert software, Box-Behnken design under response surface methodology was selected as the experimental design. Disintegration time (DT), time for 90% dissolution of LDV (LDV-T90%) and time for 90% dissolution of SBV (SBV-T90%) of the ODFs were taken as response. The films were developed using solvent casting method. The obtained films were subjected for various quality characteristic studies like differential scanning calorimetry, X-ray diffraction, tensile strength, % elongation, folding endurance, disintegration time, drug content uniformity and dissolution studies. All the formulations were found to have favorable tensile strength, % elongation and folding endurance. The DT values were found to be in the range of 37 – 139 sec.; the values of LDV-T90% and SBV-T90% were found to be in the range of 7.1 – 20.7 min. and 6.8 – 15.6 min. respectively. The results of these three responses were subjected to ANOVA studies and found that all the three formulation factors were having significant effect. The results of optimization by desirability functions approach indicated the ODFs with thickness 50µm, disintegrant at 12% w/w and plasticizer at 17.46%w/w as the optimized formulation. The ODFs prepared at this combination showed DT of 45 sec, LDV-T90% of 7.51 min. and SBV-T90% of 6.23 min. these results indicated that ODFs for LDV and SBV were successfully optimized and developed.

Mechanistic understanding of the performance of personalized 3D-printed cardiovascular polypills: A case study of patient-centered therapy

The 3D printing has become important in drug development for patient-centric therapy by combining multiple drugs with different release characteristics in a single polypill. This study explores the critical formulation and geometric variables for tailoring the release of Atorvastatin and Metoprolol as model drugs in a polypill when manufactured via pressure-assisted-microextrusion 3D printing technology. The effects of these variables on the extrudability of printing materials, drug release and other quality characteristics of polypills were studied employing a definitive screening design. The extrudability of printing materials was evaluated in terms of flow pressure, non-recoverable strain, compression rate, and elastic/plastic flow. The extrudability results helped in defining an operating space free of printing defects. The Atorvastatin compartment of polypill consisted of mesh-shaped layers while Metoprolol compartment consisted of a core surrounded by a release controlling shell with a hydrophobic septum between the two compartments.The results indicated that both the formulation and geometric variables govern the drug release of the polypill. Specifically, the use of HPMC E3 matrix, and a 2 mm distance between the strands at a weaving angle of 90° were critical in achieving the desired immediate-release profile of Atorvastatin. The core and shell design primarily determined the desired extended-release profile of Metoprolol. The carbopol and HPMC K100 concentration of 1% in the core and 10% in the shell and the number of shell layers in Metoprolol compartment were critical for achieving the desired Metoprolol dissolution. Polymer and Metoprolol content of the shell and shell-thickness affected the mechanical strength of the polypills. In conclusion, the 3D printing provides the flexibility for independently tailoring the release of different drugs in the same dosage form for patient centric therapy, and both the formulation and geometric parameters need to be optimized to achieve desired drug release.

Kinetic solubility improvement and influence of polymers on controlled supersaturation of itraconazole-succinic acid nano-co-crystals

Nano-co-crystals enhance the solubility and dissolution rate of poorly soluble drugs. The objective of this study was to obtain a better understanding of the dissolution process of nano-co-crystals and of the precipitation inhibition by various polymers. Itraconazole-succinic acid (ITZ-SUC) nano-co-crystal was chosen as model drug formulation to investigate the supersaturation and precipitation inhibition capabilities of various polymers (HPMC E5, HPMC E50, HPMCAS, HPC-SSL, PVPK30 and PVPVA64). The kinetic concentration–time profiles of nano-co-crystal were measured under non-sink conditions with in situ UV–VIS spectroscopy. HPMC E5 performed best by achieving the greatest extended supersaturation/precipitation inhibition. The precipitation inhibition capacity of HPMC E5 was proportional to its concentration. The maximum achievable supersaturation was proportional to the dissolution rate which can be modulated by the rate of supersaturation generation (i.e., addition rate or dose). Supersaturation could be prolonged significantly resulting in 2–5-fold increased area under the dissolution curves compared to nano-co-crystals alone. This effect was limited by a critical excess of undissolved particles with high specific surface area which acted as crystallization seeds resulting in faster precipitation. The study highlighted that a faster dissolution rate and the use of precipitation inhibitors were two key factors determining the extent and time of supersaturation of nano-co-crystals.

Formulation Development and In vitro Evaluation of Memantine Hydrochloride Fast Dissolving Oral Films employing different grades of Hydroxy Propyl Methyl Cellulose

The aim of this present research work is to formulate and evaluate mouth dissoving films using Memantine hydrochloride as a model drug which is used for facilitating rapid onset of action in Alzheimer’s patients who are mentally ill. The films were designed to dissolve upon contact with a wet surface, such as tongue, within a few seconds especially for these patients who are unable to swallow. In this present research work various trials were carried out using different grades of HPMC E3, E5 and E15 by solvent casting method. The prepared films were eva1uated for morphological properties, weight variation, drug content uniformity, thickness uniformity, folding endurance, surface pH, In-vitro disintegration time,In-vitro dissolution studies and stability studies of the satisfactory formulation. Films prepared using HPMC E5 and E15 showed better morphohogical properties when compred with grade E3. Best formulations F4 and F8 prepared using HPMC E5 and E15 respectively with polymer concentration 45% showed minimum disintegration time and maximum dissolution rate. A slight increase in drug dissolution rate with F8 was observed but there is no significant difference between these two formulations was identified. These findings suggest that the fast dissolving film containing Memantine is considered to be potentially useful for the treatment of Alzheimer’s where geriatric patients feel difficulty to swallow a dosage form.