Formulation Development and Optimization of Oral Thin Films of Zolpidem Tartarate

<em>The aim of the present study was to formulate and evaluate oral thin films of zolpidem tartarate. Zolpidem tartarateis used to treat insomnia. It affects chemicals in your brain that may become unbalanced and cause sleep problems (insomnia). Zolpidem tartarate oral thin films were prepared by using solvent casting method. In this method, water soluble polymer is completely dissolved in to form uniform clear viscous solution other ingredients including API are dissolved in a small portion of aqueous solvent by using a high shear processor. This viscous solution is degassed under the vacuum to remove the air bubbles. This bubble free solution is poured into a glass mold and kept in oven at 40 º-50ºC. Oral disintegrating films are prepared using three grades of polymers HPMC E5, GUAR GUM and SODIUM ALGINATE Compatibility of Zolpidem tartarate with polymers was confirmed by FT-IR studies. All the formulations were evaluated for their physical appearance, average weight and thickness, folding endurance, disintegration time, tensile strength, percentage elongation, drug content, content uniformity and in vitro drug dissolution studies. From the result, it was concluded that the fast dissolving films of Zolpidem tartarate can be made by solvent casting technique with enhanced dissolution rate and taste masking by using suitable combination of sweeteners, flavors and citric acid. The final composition optimized was drug to Guar Gum ratio of 1:1, plasticizer concentration of 15% w/w of polymer. The film had acceptable physical properties, assay and uniformity values and in vitro dissolution within 2 minutes.</em>

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Formulation Development and Characterization of controlled release core in cup matrix tablets of venlafaxine HCl

Current Drug Therapy ◽

10.2174/1574885515666200331104440 ◽

2020 ◽

Vol 15 ◽

Author(s):

Balaji Maddiboyina ◽

Vikas Jhawat ◽

Gandhi Sivaraman ◽

Om Prakash Sunnapu ◽

Ramya Krishna Nakkala ◽

...

Keyword(s):

Controlled Release ◽

Drug Release ◽

Release Rate ◽

Zero Order ◽

Water Soluble ◽

Matrix Tablets ◽

Drug Dissolution ◽

Crystalline Cellulose ◽

Hydrophobic Polymers

Background: Venlafaxine HCl is a selective serotonin reuptake inhibitor which is given in the treatment of depression. The delivery of the drug at a controlled rate can be of great importance for prolonged effect. Objective: The objective was to prepare and optimize the controlled release core in cup matrix tablet of venlafaxine HCl using the combination of hydrophilic and hydrophobic polymers to prolong the effect with rate controlled drug release. Methods: The controlled release core in cup matrix tablets of venlafaxine HCl were prepared using HPMC K5, K4, K15, HCO, IPA, aerosol, magnesium sterate, hydrogenated castor oil and micro crystalline cellulose PVOK-900 using wet granulation technique. Total ten formulations with varying concentrations of polymers were prepared and evaluated for different physicochemical parameters such FTIR analysis for drug identification, In-vitro drug dissolution study was performed to evaluate the amount of drug release in 24 hrs, drug release kinetics study was performed to fit the data in zero order, first order, Hixson–crowell and Higuchi equation to determine the mechanism of drug release and stability studies for 3 months as observed. Results: The results of hardness, thickness, weight variation, friability and drug content study were in acceptable range for all formulations. Based on the In vitro dissolution profile, formulation F-9 was considered to be the optimized extending the release of 98.32% of drug up to 24 hrs. The data fitting study showed that the optimized formulation followed the zero order release rate kinetics and also compared with innovator product (flavix XR) showed better drug release profile. Conclusion: The core-in-cup technology has a potential to control the release rate of freely water soluble drugs for single administration per day by optimization with combined use of hydrophilic and hydrophobic polymers.

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DESIGN, DEVELOPMENT, AND CHARACTERIZATION OF OROMUCOSAL WAFER OF TRAMADOL HYDROCHLORIDE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i8.25709 ◽

2018 ◽

Vol 11 (8) ◽

pp. 116

Author(s):

Rita N Wadetwar ◽

Tejaswini Charde

Keyword(s):

Drug Release ◽

Biodegradable Polymer ◽

Research Work ◽

Water Soluble ◽

Content Uniformity ◽

Onset Of Action ◽

Water Soluble Polymer ◽

Surface Ph ◽

Folding Endurance

Objective: The objective of the present work was the preparation of fast-dissolving film of tramadol HCl (TMH) using water-soluble polymer, to achieve faster onset of action, to improve patient compliance, ease of dosing, and bypass the first-pass metabolism. Methods: TMH oromucosal wafers were prepared using pullulan as natural, biodegradable polymer, and propylene glycol as plasticizer by solvent casting method. Formulation batches were prepared using 32 full-factorial designs. The prepared TMH oromucosal wafers were characterized for morphology, uniformity of weight, drug content, folding endurance, in vitro disintegration time (DT), % moisture content, surface pH, in vitro % drug release, ex vivo permeation studies, compatibility studies (differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray diffraction), and stability studies.Results: Optimized batch of mouth-dissolving film of TMH containing pullulan as polymer showed 98.67±0.11% drug release at 6 min. It showed better folding endurance 88 No. of folds, in vitro DT 5.11 s, surface pH 6.84±0.12 pH, thickness 0.17±0.11 mm, and percentage content uniformity 98.45±0.48%. Stability studies carried out for the best formulation FDF5 revealed that the formulation was stable.Conclusion: The results obtained in this research work clearly indicated a promising potential of fast-dissolving oral films using natural biodegradable polymer, pullulan which gave rapid drug delivery and rapid onset of action of centrally acting drug, TMH for patients suffering from pain.

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Formulation Development and Evaluation of Multiple Unit Pellet System of Tamsulosin Hydrochloride

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00927 ◽

2021 ◽

pp. 5319-5324

Author(s):

Gavaskar Basani ◽

Madhusudan Rao Yamsani ◽

Ramya Sri Sura

Keyword(s):

Extended Release ◽

Drug Loading ◽

Prostate Gland ◽

Water Soluble ◽

Formulation Development ◽

Water Soluble Polymer ◽

Multiple Unit ◽

Binder Concentration ◽

Extrusion Spheronization ◽

Drug Coating

The aim of current work was to grow extended release multiple unit pellets of Tamsulosin Hydrochloride, is an alpha-blocker, used for the healing of the symptoms of a prostate gland condition called BPH (benign prostatic hyperplasia) by extrusion- spheronization (E/S) and solution/suspension layering (S/S) method. In the Extrusion-Spheronization, A ratio of 75:25, 67:33, 64:36 Tamsulosin Hydrochloride and Microcrystalline cellulose were mixed for making drug pellets and extended release (ER) coating was performed in fluidized bed processor (FBP) by solution/suspension layering with Ethyl cellulose (aqueous. dispersion, 4 cps and 7 cps) and Hypromellose (5cps) with different ratios % weight buildups accordingly. In the Solution/suspension layering (S/S) method, Tamsulosin Hydrochloride drug pellets were prepared by layering onto MCC spheres in FBP. These drug pellets were further coated for extended release with HPMC, 5cps and EC, 7cps. In drug coating stage, drug and different binder (Hypromellose, 5 cps) concentrations 8, 10, 12, 14 mg/unit were coated onto the cores for optimization of binder concentration. The weight of MCC spheres were optimized for further formulations. For all the drug coated pellets, ER coating was given with EC, 7cps and HPMC, 5 cps at a coating level of 8% weight by weight. In the extrusion- spheronization (E/S) Optimization of Drug pellets: Among the trials TD3 (Tamsulosin HCl and MCC) showed good mechanical strength with better yield due to increased MCC concentration. Optimization of Extended Release Coating: Optimized TD3 drug pellets were coated with ER coating using water insoluble polymer (Aq.EC 25% dispersion/ EC, 4cps/ EC, 7cps) and water soluble polymer (HPMC, 5cps). Among these polymers, extended release coating was optimized (TD3E14) with the combination of EC, 7cps and HPMC, 5cps at 8% weight build up. In the Solution/Suspension layering: Optimization of binder concentration in drug coating stage: HPMC, 5cps with 12 mg/unit for TF7 was optimized based on %yield. Optimization of MCC spheres in drug coating stage in formulation of ER pellets with different weight drug pellets: The weight of MCC spheres (160, 170, 180, 190 mg/unit) used in the drug coating stage with binder HPMC, 5cps (12 mg/unit). These drug pellets were given with ER coating at 8% weight buildup by using EC, 7cps and HPMC, 5cps. Among these trials, TF7E7 was optimized. Based on the investigations of the present study, conclusions was. formulating low dose, high soluble, BCS class I drug- Tamsulosin Hydrochloride ER formulation by extrusion-spheronization showed flexibility for batch processing and cost effectiveness while solution/suspension layering was process feasible but time consuming due to high drug loading.

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Energy-Saving Electrospinning with a Concentric Teflon-Core Rod Spinneret to Create Medicated Nanofibers

Polymers ◽

10.3390/polym12102421 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2421 ◽

Cited By ~ 1

Author(s):

Shixiong Kang ◽

Shicong Hou ◽

Xunwei Chen ◽

Deng-Guang Yu ◽

Lin Wang ◽

...

Keyword(s):

Energy Saving ◽

Energy Savings ◽

Ex Vivo ◽

Low Cost ◽

Electrospun Nanofibers ◽

Electrospinning Process ◽

Water Soluble ◽

Drug Dissolution ◽

Core Rod

Although electrospun nanofibers are expanding their potential commercial applications in various fields, the issue of energy savings, which are important for cost reduction and technological feasibility, has received little attention to date. In this study, a concentric spinneret with a solid Teflon-core rod was developed to implement an energy-saving electrospinning process. Ketoprofen and polyvinylpyrrolidone (PVP) were used as a model of a poorly water-soluble drug and a filament-forming matrix, respectively, to obtain nanofibrous films via traditional tube-based electrospinning and the proposed solid rod-based electrospinning method. The functional performances of the films were compared through in vitro drug dissolution experiments and ex vivo sublingual drug permeation tests. Results demonstrated that both types of nanofibrous films do not significantly differ in terms of medical applications. However, the new process required only 53.9% of the energy consumed by the traditional method. This achievement was realized by the introduction of several engineering improvements based on applied surface modifications, such as a less energy dispersive air-epoxy resin surface of the spinneret, a free liquid guiding without backward capillary force of the Teflon-core rod, and a smaller fluid–Teflon adhesive force. Other non-conductive materials could be explored to develop new spinnerets offering good engineering control and energy savings to obtain low-cost electrospun polymeric nanofibers.

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Different BCS Class II Drug-Gelucire Solid Dispersions Prepared by Spray Congealing: Evaluation of Solid State Properties and In Vitro Performances

Pharmaceutics ◽

10.3390/pharmaceutics12060548 ◽

2020 ◽

Vol 12 (6) ◽

pp. 548 ◽

Cited By ~ 1

Author(s):

Serena Bertoni ◽

Beatrice Albertini ◽

Nadia Passerini

Keyword(s):

Solid State ◽

Drug Carrier ◽

Solid Dispersions ◽

Class Ii ◽

Water Soluble ◽

Drug Dissolution ◽

Crystalline Solid ◽

Dissolution Behavior ◽

Bcs Class Ii

Delivery of poorly water soluble active pharmaceutical ingredients (APIs) by semi-crystalline solid dispersions prepared by spray congealing in form of microparticles (MPs) is an emerging method to increase their oral bioavailability. In this study, solid dispersions based on hydrophilic Gelucires® (Gelucire® 50/13 and Gelucire® 48/16 in different ratio) of three BCS class II model compounds (carbamazepine, CBZ, tolbutamide, TBM, and cinnarizine, CIN) having different physicochemical properties (logP, pKa, Tm) were produced by spray congealing process. The obtained MPs were investigated in terms of morphology, particles size, drug content, solid state properties, drug-carrier interactions, solubility, and dissolution performances. The solid-state characterization showed that the properties of the incorporated drug had a profound influence on the structure of the obtained solid dispersion: CBZ recrystallized in a different polymorphic form, TBM crystallinity was significantly reduced as a result of specific interactions with the carrier, while smaller crystals were observed in case of CIN. The in vitro tests suggested that the drug solubility was mainly influenced by carrier composition, while the drug dissolution behavior was affected by the API solid state in the MPs after the spray congealing process. Among the tested APIs, TBM-Gelucire dispersions showed the highest enhancement in drug dissolution as a result of the reduced drug crystallinity.

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In Vitro and In Vivo Evaluation of Olmesartan Medoxomil Microcrystals and Nanocrystals: Preparation, Characterization, and Pharmacokinetic Comparison in Beagle Dogs

Current Drug Delivery ◽

10.2174/1567201816666190627143214 ◽

2019 ◽

Vol 16 (6) ◽

pp. 500-510

Author(s):

Rong Chai ◽

Hailing Gao ◽

Zhihui Ma ◽

Meng Guo ◽

Qiang Fu ◽

...

Keyword(s):

Particle Size ◽

Oral Bioavailability ◽

Olmesartan Medoxomil ◽

Water Soluble ◽

Size Reduction ◽

Drug Dissolution ◽

Beagle Dogs ◽

Enhanced Solubility

Background: Olmesartan medoxomil (OLM) is a promising prodrug hydrolyzed to olmesartan (OL) during absorption from the gastrointestinal tract. OL is a selective angiotensin II receptor antagonist, with high drug resistance and low drug interaction. However, OLM has low solubility and low bioavailability. Therefore, it is extremely urgent to reduce the drug particle size to improve its biological bioavailability. Objective: The aim of the study was to improve the oral bioavailability of poorly water-soluble olmesartan medoxomil (OLM) by using different particle size-reduction strategies. Method: Raw drug material was micronized or nanosized by either jet or wet milling processes, respectively. The particle sizes of the prepared nanocrystals (100-300 nm) and microcrystals (0.5-16 μm) were characterized by DLS, SEM, and TEM techniques. Solid state characterization by XPRD and DSC was used to confirm the crystalline state of OLM after the milling processes. Results: We demonstrated that OLM nanocrystals enhanced solubility and dissolution in the non-sink condition in which high sensitivity was found in purified water. After 1 h, 65.4% of OLM was dissolved from nanocrystals, while microcrystals and OLMETEC® only showed 37.8% and 31.9% of drug dissolution, respectively. In the pharmacokinetic study using Beagle dogs, an increase in Cmax (～2 fold) and AUC (～1.6 fold) was observed after oral administration of OLM nanocrystals when compared to microcrystals and reference tablets, OLMETEC®. In contrast, OLM microcrystals failed to improve the oral bioavailability of the drugs. Conclusion: Particles size reduction to nano-scale by means of nanocrystals technology significantly increased in vitro dissolution rate and in vivo oral bioavailability of OLM.

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Effects of Hydrophilic Carriers on Structural Transitions and In Vitro Properties of Solid Self-Microemulsifying Drug Delivery Systems

Pharmaceutics ◽

10.3390/pharmaceutics11060267 ◽

2019 ◽

Vol 11 (6) ◽

pp. 267 ◽

Cited By ~ 5

Author(s):

Tao Yi ◽

Jifen Zhang

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Water Soluble ◽

Drug Dissolution ◽

Commercial Application ◽

Simulated Gastric Fluid ◽

Structural Transitions

Self-microemulsifying drug delivery systems (SMEDDS) offer potential for improving the oral bioavailability of poorly water-soluble drugs. However, their susceptibilities during long term storage and in vivo precipitation issues limit their successful commercial application. To overcome these limitations, SMEDDS can be solidified with solid carriers, thus producing solid self-microemulsifying drug delivery systems (S-SMEDDS). In this study, effects of various hydrophilic carriers on structural transitions and in vitro properties of S-SMEDDS were investigated in order to set up in vitro methods for screening out appropriate carriers for S-SMEDDS. Liquid SMEDDS was prepared and characterized using nimodipine as a model drug. The effects of various hydrophilic carriers on internal microstructure and solubilization of SMEDDS were investigated by conductivity measurement and in vitro dispersion test. The results showed that hydrophilic carriers including dextran 40, maltodextrin and PVP K30 seemed to delay the percolation transition of SMEDDS, allowing it to maintain a microstructure that was more conducive to drug dissolution, thus significantly increasing the solubilization of nimodipine in the self-microemulsifying system and decreasing drug precipitation when dispersed in simulated gastric fluid. S-SMEDDS of nimodipine were prepared by using spray drying with hydrophilic carriers. The effects of various hydrophilic carriers on in vitro properties of S-SMEDDS were investigated by using SEM, DSC, PXRD and in vitro dissolution. The results showed that properties of hydrophilic carriers, especially relative molecular mass of carriers, had obvious influences on surface morphologies of S-SMEDDS, reconstitution of microemulsion and physical state of nimodipine in S-SMEDDS. Considering that in vitro properties of S-SMEDDS are closely related to their pharmacokinetic properties in vivo, the simple and economical in vitro evaluation methods established in this paper can be used to screen solid carriers of S-SMEDDS well.

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Polyaniline: Thin films and colloidal dispersions (IUPAC Technical Report)

Pure and Applied Chemistry ◽

10.1351/pac200577050815 ◽

2005 ◽

Vol 77 (5) ◽

pp. 815-826 ◽

Cited By ~ 178

Author(s):

Jaroslav Stejskal ◽

Irina Sapurina

Keyword(s):

Thin Films ◽

Dispersion Polymerization ◽

Average Particle Size ◽

Colloidal Dispersions ◽

Water Soluble ◽

Average Particle ◽

Water Soluble Polymer ◽

Ammonium Peroxydisulfate ◽

Technical Report

Several workers from various institutions in six countries have prepared thin films and colloidal polyaniline dispersions. The films were produced in situ on glass supports during the oxidation of anilinium chloride with ammonium peroxydisulfate in water. The average thickness of the films, assessed by optical absorption, was 125 ± 9 nm, and the conductivity of films was 2.6 ± 0.7 S cm–1. Films prepared in 1 mol l–1 HCl had a similar thickness, 109 ± 10 nm, but a higher conductivity, 18.8 ± 7.1 S cm–1. Colloidal polyaniline particles stabilized with a water-soluble polymer, poly(N-vinylpyrrolidone) [poly(1-vinylpyrrolidin-2-one)], have been prepared by dispersion polymerization. The average particle size, 241 ± 50 nm, and polydispersity, 0.26 ± 0.12, have been determined by dynamic light scattering. The preparation of these two supramolecular polyaniline forms was found to be well reproducible.

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