scholarly journals Formulation and optimization of gastroretentive bilayer tablets of calcium carbonate using D-optimal mixture design

e-Polymers ◽  
2021 ◽  
Vol 21 (1) ◽  
pp. 057-071
Author(s):  
Manasa Moganti ◽  
Shivakumar H. Nanjappa
Keyword(s):  
Calcium Carbonate ◽  
Optimization Technique ◽  
Lag Time ◽  
Mixture Design ◽  
Burst Release ◽  
Bilayer Tablets ◽  
Absorption Window ◽  
Upper Gastrointestinal ◽  
Gastric Retention Time

Abstract Gastroretentive bilayer tablets of calcium carbonate (CC) were developed using D-optimal mixture design. The effect of formulation factors such as levels of HPMC K100 M (X1), sodium bicarbonate (X2), and HPMC E15 LV (X3) on responses like floating lag time (R1) and release of CC at 1 h (R2) and 6 h (R3) was elucidated. The optimized formulations developed by numerical optimization technique were found to have short floating lag time (2.85 ± 0.98 min), minimum burst release (27.02 ± 1.18%), and controlled yet near complete release (88.98 ± 2.75%) at 6 h. In vivo radiographic studies in rabbits indicated that optimized batch displayed a mean gastric retention time (GRT) of 5.5 ± 1 h which was significantly prolonged (P < 0.05) compared to the conventional tablets that displayed a GRT of less than 1 h. The studies proved that the gastroretentive tablets can be a promising platform to improve bioavailability of nutrients having absorption window in upper gastrointestinal tract.

scholarly journals Application of Design of Experiment for Polyox and Xanthan Gum Coated Floating Pulsatile Delivery of Sumatriptan Succinate in Migraine Treatment

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Swati C. Jagdale ◽  
Chandrakala R. Pawar
Keyword(s):  
Design Of Experiment ◽  
Xanthan Gum ◽  
Dosage Form ◽  
Lag Time ◽  
Migraine Treatment ◽  
Burst Release ◽  
Night Time ◽  
Sumatriptan Succinate

Migraine follows circadian rhythm in which headache is more painful at the awakening time. This needs administration of dosage form at night time to release drug after lag period when pain gets worse. Sumatriptan succinate is a drug of choice for migraine. Sumatriptan succinate has bitter taste, low oral bioavailability, and shorter half-life. Present work deals with application of design of experiment for polyox and xanthan gum in development of press coated floating pulsatile tablet. Floating pulsatile concept was applied to increase gastric residence of the dosage form. Burst release was achieved through immediate release tablet using crospovidone as superdisintegrant (10%). Pulse lag time was achieved using swellable polymer polyox WSR205 and xanthan gum. 32experimental design was applied. Optimized formulation was evaluated for physical characteristics andin-vitroandin-vivostudy. From results, it can be concluded that optimized batch F8 containing polyox WSR205 (72.72%) and xanthan gum (27.27%) of total weight of polymer has shown floating lag time of 55 ± 2 sec, drug content of 100.35 ± 0.4%, hardness of 6 ± 0.1 Kg/cm2, and 98.69 ± 2% drug release in pulse manner with lag time of 7 ± 0.1 h. Optimized batch showed prolong gastric residence which was confirmed byin-vivoX-ray study.

A Novel Drug Delivery System: Floating Microspheres in the Development of Gastroretentive Drug Delivery System

2021 ◽  
pp. 86-92
Author(s):  
Vandana Gupta ◽  
Jaya Singh
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Medication Delivery ◽  
Long Time ◽  
Drug Waste ◽  
Novel Drug ◽  
Absorption Window ◽  
Gastric Retention Time

Gastric emptying is a complicated process in the human body because it is very inconstant, resulting in ambiguous in vivo drug delivery system efficacy. To combat this variability, scientists have been working on developing a regulated medication delivery system with a long gastric residence period. This review article on gastroretentive drug delivery systems (GRDDS) focuses on numerous gastroretentive approaches that have recently emerged as a leading methodology in the field of site-specific orally administered controlled release drug administration. Gastroretentive medicines come in a variety of forms on the market, including tablets, granules, capsules, floating microspheres, laminated films, and powders. Floating microspheres are currently garnering more attention than previous techniques because of their benefits, which include more consistent drug absorption and a lower risk of local discomfort. The primary goal of this method is to increase gastric retention time in the GIT, which is defined as more than 12 hours in the stomach with an absorption window in the upper small intestine. Longer stomach retention improves bioavailability, reduces drug waste, and boosts solubility for medications that are less soluble in a high pH environment. The medicines are released into the stomach for a long time and consistently thanks to the floating microsphere systems. The current study compiles the most recent research on the techniques of production, characterization, and numerous aspects that impact the performance of floating microspheres for oral administration.

Development and Evaluation of Floating Pulsatile Drug Delivery System Using Meloxicam

2017 ◽  
Vol 7 (04) ◽  
Author(s):  
ShirishaG. Suddala ◽  
S. K. Sahoo ◽  
M. R. Yamsani
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Drug Release ◽  
Drug Delivery System ◽  
Delivery System ◽  
Lag Time ◽  
Oral Dosage ◽  
Lag Phase ◽  
Pulsatile Drug Delivery

Objective: The objective of this research work was to develop and evaluate the floating– pulsatile drug delivery system (FPDDS) of meloxicam intended for Chrono pharmacotherapy of rheumatoid arthritis. Methods: The system consisting of drug containing core, coated with hydrophilic erodible polymer, which is responsible for a lag phase for pulsatile release, top cover buoyant layer was prepared with HPMC K4M and sodium bicarbonate, provides buoyancy to increase retention of the oral dosage form in the stomach. Meloxicam is a COX-2 inhibitor used to treat joint diseases such as osteoarthritis and rheumatoid arthritis. For rheumatoid arthritis Chrono pharmacotherapy has been recommended to ensure that the highest blood levels of the drug coincide with peak pain and stiffness. Result and discussion: The prepared tablets were characterized and found to exhibit satisfactory physico-chemical characteristics. Hence, the main objective of present work is to formulate FPDDS of meloxicam in order to achieve drug release after pre-determined lag phase. Developed formulations were evaluated for in vitro drug release studies, water uptake and erosion studies, floating behaviour and in vivo radiology studies. Results showed that a certain lag time before drug release which was due to the erosion of the hydrophilic erodible polymer. The lag time clearly depends on the type and amount of hydrophilic polymer which was applied on the inner cores. Floating time and floating lag time was controlled by quantity and composition of buoyant layer. In vivo radiology studies point out the capability of the system of longer residence time of the tablets in the gastric region and releasing the drug after a programmed lag time. Conclusion: The optimized formulation of the developed system provided a lag phase while showing the gastroretension followed by pulsatile drug release that would be beneficial for chronotherapy of rheumatoid arthritis and osteoarthritis.

Internal and External Triggering Mechanism of “Smart” Nanoparticle-Based DDSs in Targeted Tumor Therapy

2018 ◽  
Vol 24 (15) ◽  
pp. 1639-1651 ◽  
Author(s):  
Xian-ling Qian ◽  
Jun Li ◽  
Ran Wei ◽  
Hui Lin ◽  
Li-xia Xiong
Keyword(s):  
Targeted Delivery ◽  
Tumor Therapy ◽  
Burst Release ◽  
Tumor Site ◽  
Chemotherapeutic Drugs ◽  
Triggering Mechanism ◽  
Triggering Factors ◽  
Or Genes

Background: Anticancer chemotherapeutics have a lot of problems via conventional Drug Delivery Systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: “passive”, “active”, and “smart” targeting. Objective: To summarize the mechanisms of various internal and external “smart” stimulating factors on the basis of findings from in vivo and in vitro studies. Method: A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Results: Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), “smart” DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. Conclusion: In this review article, we summarize and classify the internal and external triggering mechanism of “smart” nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding.

Utilization of a Single Experimental Design for the Optimization of Furosemide Modified-Release Tablet Formulations

2019 ◽  
Vol 16 (10) ◽  
pp. 931-939
Author(s):  
Marilena Vlachou ◽  
Angeliki Siamidi ◽  
Yannis Dotsikas
Keyword(s):  
Experimental Design ◽  
Drug Release ◽  
Burst Release ◽  
Dissolution Profile ◽  
Modified Release ◽  
Lactose Monohydrate ◽  
Bilayer Tablets ◽  
Combined Design ◽  
Tablet Formulations ◽  
Optimal Combined Design

Background: The loop diuretic drug furosemide is widely used for the treatment of edema in various conditions, such as pulmonary, cardiac and hepatic edema, as well as cardiac infarction. Furosemide, due to its poor water solubility and low bioavailability after oral administration of conventional dosage form, is categorized as class IV in the biopharmaceutical classification system. Objective: In the case of furosemide, this release profile is responsible for various physiological problems, acute diuresis being the most serious. This adverse effect can be circumvented by the modified release of furosemide from tablet formulations compared to those forms designed for immediate release. Method: In this report, a D-optimal combined experimental design was applied for the development of furosemide containing bilayer and compression coated tablets, aiming at lowering the drug’s burst release in the acidic environment of the stomach. A D-optimal combined design was selected in order to include all requirements in one design with many levels for the factors examined. The following responses were selected as the ones reflecting better criteria for the desired drug release: dissolution at 120 min (30-40%), 300 min (60-70%) and 480 min >95%. The new formulations, suggested by the Doptimal combined design, incorporated different grades of Eudragit ® polymers (Eudragit® E100 and Eudragit® L100-55), lactose monohydrate and HPMC K15M. The dissolution profile of furosemide from these systems was probed via in vitro dissolution experiments in buffer solutions simulating the pH of the gastrointestinal tract. Results: The results indicate that the use of Eudragit® E100 in conjunction with lactose monohydrate led to 21.32-40.85 % drug release, in the gastric medium, in both compression-coated and bilayer tablets. This is lower than the release of the mainstream drug Lasix® (t=120 min, 44.5% drug release), implying longer gastric retention and drug waste minimization. Conclusion: Furosemide’s release in the intestinal environment, from compression coated tablets incorporating Eudragit® L100-55 and HPMC K15M in the inner core or one of the two layers of the bilayer tablets, was delayed, compared to Lasix®

Desirability Based Optimization of New Mesalazine Modified Release Formulations: Compression Coated Tablets and Mini Tablets in Capsules

2020 ◽  
Vol 17 (2) ◽  
pp. 114-123
Author(s):  
Marilena Vlachou ◽  
Angeliki Siamidi ◽  
Yannis Dotsikas
Keyword(s):  
Gastrointestinal Tract ◽  
Experimental Design ◽  
Desirability Function ◽  
Symptomatic Treatment ◽  
Mixture Design ◽  
Upper Gastrointestinal Tract ◽  
Modified Release ◽  
Aminosalicylic Acid ◽  
Colonic Delivery ◽  
Upper Gastrointestinal

Background: Mesalazine (5-aminosalicylic acid, 5-ASA) is a drug substance with an antiinflammatory activity, which is mainly used in the symptomatic treatment of diseases, such as Ulcerative Colitis, the Crohn's disease and the idiopathic inflammatory bowel disease. Mesalazine exerts its effect locally in the inflamed area of the intestine and not through systematic absorption, therefore the investigation of its release characteristics from solid pharmaceutical formulations is of great importance. Objective: The development of novel mesalazine modified release formulations with improved properties, regarding drug release in the gastrointestinal tract, by utilisation of the Design of Experiments (DoE) approach. Methods: D-optimal experimental design was applied. A Simplex Lattice mixture design was used for the development of suitable capsules containing 4 mini tablets and a D-optimal mixture design was used for compression-coated tablets, with the following characteristics: ≤10% release in 2 h, to minimize its degradation in the upper gastrointestinal tract, 20-40% release in 5 h for mesalazine administration in the small intestine, and quantitative release in 12 h for colonic delivery. The dissolution experiments were conducted in gastrointestinal-like fluids and pectinases to simulate the pectinolytic enzymes present in the colon. Results: The optimal compositions were reached via the desirability function, as a compromise to the different responses. The optimal solutions for both formulations led to colon-specific delivery of the active substance with minimal 5-ASA release in the upper gastrointestinal tract and appeared to conform with the pre-determined characteristics. Hard gelatin capsules, when filled with mini-tablets led to the aimed modified release profile, having sigmoidal characteristics and compression coated tablets led to colonic delivery. Conclusion: Two novel mesalazine formulations were developed with the desirable colonic release, by conducting a minimal number of experiments, as suggested by DoE experimental design.

Cytotoxicity Studies of Curcumin Loaded-Cockle Shell-Derived Calcium Carbonate Nanoparticles

2019 ◽  
Vol 09 ◽  
Author(s):  
Maryam Muhammad Mailafiya ◽  
Mohamad Aris Mohd Moklas ◽  
Kabeer Abubakar ◽  
Abubakar Danmaigoro ◽  
Samaila Musa Chiroma ◽  
...  
Keyword(s):  
Calcium Carbonate ◽  
Safety Margin ◽  
Bone Diseases ◽  
In Vivo Studies ◽  
Normal Cells ◽  
Cytotoxicity Studies ◽  
Standard Techniques ◽  
Cockle Shell

Background: Cockle shell-derived calcium carbonate nanoparticles (CSCaCO3NP) are natural biogenic inorganic material that is used in drug delivery mainly as a bone-remodeling agent as well as a delivery agent for various therapeutics against bone diseases. Curcumin possess wide safety margin and yet puzzled with the problem of poor bioavailability due to insolubility. Propounding in vitro and in vivo studies on toxicity assessments of newly synthesized nanoparticles are ongoing to overcome some crucial challenges regarding their safety administration. Nanotoxicology has paved ways for concise test protocols to monitor sequential events with regards to possible toxicity of newly synthesized nanomaterials. The development of nanoparticle with no or less toxic effect has gained tremendous attentions. Objective: This study aimed at evaluating the in vitro cytotoxic effect of curcumin-loaded cockle shell-derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) and assessing its biocompatibility on normal cells using standard techniques of WST’s assay. Method: Standard techniques of WST’s assay was used for the evaluation of the biocompatibility and cytotoxicity. Result: The result showed that CSCaCO3NP and Cur-CSCaCO3NP possess minimal toxicity and high biocompatibility on normal cells even at higher dose of 500 µg/ml and 40 µg/ml respectively. Conclusion: CSCaCO3NP can be termed an excellent non-toxic nanocarrier for curcumin delivery. Hence, curcumin loaded cockle shell derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) could further be assessed for various in vivo and in vitro therapeutic applications against various bone related ailments.

scholarly journals Effects of bisphosphonate and calcium carbonate on normal aortic valve and cholecalciferol induced in vivo rabbit aortic stenosis model

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Okutucu ◽  
C Sabanoglu ◽  
A Saglam Ayhan ◽  
E Tulumen ◽  
H Aksoy ◽  
...  
Keyword(s):  
Calcium Carbonate ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Calcium Supplementation ◽  
Group Iv ◽  
Histopathologic Examination ◽  
Group V ◽  
Group I ◽  
Alendronate Treatment

Abstract Background Calcific aortic valve disease (CAVD) is the most common valvular heart disease. Bisphosphonates are stable analogs of pyrophosphates and commonly prescribed in the treatment of osteoporosis. The effects of bisphosphonate treatment on CAVD are not clearly known and there are inconsistent results. Similarly, the effect of calcium supplementation on CAVD remains controversial. Purpose The aim of this study was to assess the effects of bisphosphonate therapy on the normal aortic valve and vitamin D induced in vivo rabbit aortic stenosis (AS) model. Methods The impact of calcium supplementation on the rabbit AS model was also evaluated. A total of 30 New Zealand white rabbits were divided into five equal groups: no treatment (Group I); 25,000 IU/day vitamin D3 (cholecalciferol) (Group II, rabbit AS model); 25,000 IU/day cholecalciferol plus 2500 mg/day calcium carbonate (Group III); 20 μg/kg/week intravenous alendronate (Group IV) and 25,000 IU/day cholecalciferol plus 2500 mg/day calcium carbonate plus 20μg/kg/week alendronate (Group V). Echocardiography was performed at baseline and after 12 weeks of treatment. The left ventricular mass index (LVMI), aortic valve area (AVA), transvalvular velocities and gradients were recorded. Radiologic and histopathologic examination was performed at the end of the 12th week. Control animals displayed no abnormalities of the aortic valve. Results There was no echocardiographic change in Group IV. In Groups II, III and V, there was a significant decrease in AVA and increases in transvalvular velocities and gradients. However, these stenotic changes were significantly prominent in Group V (p=0.001 for all, via repeated measures ANOVA). Moreover, LVMI was only increased in Group V (p&lt;0.05). Calcification of aortic valvar complex was detected in 14 (46.7%) cases by radiologic imaging and 10 (33.3%) cases by histopathologic examination. Most frequent calcification was found in Group V (5 for each method, 83.3%). Agatston, volume and equivalent mass scores of calcific foci in Group V were significantly higher than other groups (p&lt;0.05 for all). There was no significant difference between groups regarding with presence of osteoclasts in calcific foci. Conclusion Calcium supplementation has no effect on the in vivo rabbit AS model. Alendronate treatment aggravates the stenosis and increases the calcification in the rabbit AS model. Alendronate treatment has no effect on the normal valve in which there was no osteogenesis and osteoclastogenesis. Based on these findings, in patients with CAVD, alendronate treatment should be given with regular echocardiographic follow-up or may not be preferred. Central figure Funding Acknowledgement Type of funding source: None

scholarly journals Applicability of Gum Karaya in the Preparation and in Vitro Evaluation of Losartan Potassium as Chronotherapeutic Drug Delivery System

2015 ◽  
Vol 7 (1-2) ◽  
pp. 65-74
Author(s):  
K. Latha ◽  
V. V. Srikanth ◽  
S. A. Sunil ◽  
N. R. Srinivasa ◽  
M. U. Uhumwangho ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tensile Strength ◽  
Drug Delivery System ◽  
Delivery System ◽  
Lag Time ◽  
Losartan Potassium ◽  
In Vitro Dissolution ◽  
Burst Release ◽  
Gum Karaya

The objective of this investigation is to study the applicability of gum karaya, the natural gum for the preparation and in vitro evaluation of losartan potassium, as Chronotherapeutic Drug Delivery System (ChDDS). The compression-coated timed-release tablets (CCT) containing losartan potassium in the core tablet were prepared by dry coating technique with different ratios of gum karaya as the outer coat. The parameters investigated were tensile strength, friability, in vitro dissolution studies and drug concentration. The optimized formulation was further characterized by powder XRD and FTIR to investigate interactions and no interactions observed. The tensile strength and friability of all the CCT were between 1.06-1.23 MN/m2 and < 0.3% respectively.  All the CCT showed a clear lag time before a burst release of drug. However, the lag time of drug release increased as the amount of gum karaya in the outer layer increased. For instance, the lag time of LGK1, LGK2, LGK3, LGK4, LGK5, LGK6 and LGK7 were 16, 10.5, 5.5, 3, 2, 1.5 and 0.5 hrs respectively.  The drug content of all the CCT was >98%. Formulation LGK3 was taken as an optimized formulation which can be exploited to achieve ChDDS of losartan potassium for the treatment of hypertension. 

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