In Vitro Dissolution Evidence for Sustained and Prolonged Release of Vitamin C in a Phosphatidyl Choline-Enriched Lipid Encapsulation

Abstract Objectives In vitro dissolution tests are valuable first-step tools in the development of bioavailable delivery systems, making it possible to assess the performance of novel technologies in releasing active ingredients through the amount dissolved in a dissolution medium. The objective of this study was to evaluate whether phosphatidyl choline-enriched lipid encapsulation releases the majority of vitamin C as ascorbic acid past the stomach in a standard in vitro dissolution procedure and to assess the release profile. Methods A novel phosphatidyl choline-enriched lipid encapsulation that is solid at room temperature was tested for dissolution in a standard dissolution apparatus according to compendial United States Pharmacopeia methods, as per Good Manufacturing Practices for dietary supplements. One serving (included 1000 mg ascorbic acid) was placed into vessels containing simulated gastric fluid (0.1 M HCl) for 120 minutes then changed to simulated intestinal fluid (buffered 2% sodium lauryl sulfate, pH 6.8) for an additional 360 minutes. Aliquots were tested for ascorbic acid concentration at 8 time points by titration. The data was compared with 1000 mg of regular ascorbic acid in a capsule format. Results The phosphatidyl choline-enriched lipid encapsulation released 36% of the vitamin C at 2 hours in the acid phase and released 56% at 3 hours, 67% at 4 hours, 85% at 6 hours and 98% at 8 hours in the intestinal phase. Regular vitamin C filled capsules released 100% of the vitamin C at 30 minutes. Conclusions The dissolution results indicated that phosphatidyl choline-enriched lipid encapsulation can pass the stomach and release the majority of vitamin C in the small intestine. The encapsulation demonstrated a sustained and prolonged release of vitamin C over an 8 hour period. The release profile observed in this in vitro study suggests phosphatidyl choline-enriched lipid encapsulation may improve nutrient absorption and bioavailability which requires further testing including human clinical trials. Funding Sources This study was supported by Lonza (Greenwood, SC) and Ritual (Natals Inc, Los Angeles, CA).

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In Vitro Dissolution Evidence for Delivering Multiple Vitamin-Mineral Ingredients past the Stomach by Novel Capsule Delivery System (P24-009-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.p24-009-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Luke Bucci ◽

Mastaneh Sharafi ◽

Nima Alamdari

Keyword(s):

Absorption Spectrometry ◽

Gastric Fluid ◽

Water Soluble ◽

In Vitro Dissolution ◽

Magnesium Concentration ◽

Simulated Gastric Fluid ◽

Lauryl Sulfate ◽

Simulated Intestinal Fluid ◽

Tablet Disintegration

Abstract Objectives The ability of a novel beadlet-in-oil, gastric-resistant, vegetarian capsule containing a multiple vitamin-mineral (MVM) composition to deliver capsule contents past the stomach was tested by standard in vitro tablet disintegration procedures using magnesium as the marker of capsule contents dissolution. Methods A novel capsule design using a gastric-resistant vegetarian hypromellose/gellan gum capsule (DRcaps®, Capsugel®) was tested for disintegration in a standard tablet disintegration apparatus according to compendial United States Pharmacopeia methods, as per Good Manufacturing Practices for dietary supplements. The MVM ingredients were encapsulated into size 0 Vcaps® (hypromellose with no gastric acid resistance) and DRcaps®. Individual capsules were placed into chambers containing simulated gastric fluid (0.1 M HCl) for 120 minutes then changed to simulated intestinal fluid (buffered 2% sodium lauryl sulfate, pH 6.0) for an additional 300 minutes. Aliquots were tested for magnesium concentration at ten time points by atomic absorption spectrometry. Results Magnesium was contained inside coated beadlets along with ferrous bisglycinate, methylcobalamin, 5-methyltetrahydrofolate, calcium fructoborate and cellulose. Vcaps® released 50% of the magnesium between 30–45 minutes and all by 60 minutes in the acid phase. DRcaps® released 25% of the magnesium at 45 minutes, and 43% at 120 minutes, followed by slow, steady release of the remaining magnesium by 420 minutes. Conclusions These dissolution profiles reproduce the known, rapid disintegration profile of Vcaps® when wetted. DRcaps® released the majority of their contents after the pH was changed to intestinal conditions, and then the beadlets released the water-soluble ingredients (magnesium) in a linear manner over a two hour period. Since normal stomach emptying of DRcaps® without a meal is less than 20–30 minutes (previously shown), DRcap® MVMs bypass the stomach almost completely to release ingredients in the small intestine. Thus, a novel, beadlet-in-oil, gastric-resistant capsule delivered its contents past the stomach. These properties have the ability to improve tolerability and thus, compliance with users. Funding Sources Capsugel®, Greenwood, SC, conducted this study for Ritual. Supporting Tables, Images and/or Graphs

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Effects of coating on the release profile of drug combination from hydrophilic matrix pellets

Stamford Journal of Pharmaceutical Sciences ◽

10.3329/sjps.v2i2.5824 ◽

1970 ◽

Vol 2 (2) ◽

pp. 53-58

Author(s):

Muhammad Shahidul Islam ◽

Md Moniruzzaman ◽

Ruknuzzaman Rony ◽

Tasnuva Haque

Keyword(s):

Ascorbic Acid ◽

Ferrous Sulfate ◽

Ferrous Sulphate ◽

Film Coating ◽

Release Profile ◽

In Vitro Dissolution ◽

Pharmaceutical Sciences ◽

Coating Composition ◽

Pan Coater

In this work zinc sulfate, ferrous sulfate and ascorbic acid was formulated on the same pellet by combination pelletization technique and their and in vitro dissolution studies were performed by using United States Pharmacopoeia (USP) apparatus type II. In addition, effect of different types of polymers, formulation variables and variations in coating composition on the release of drug were studied. The desired release profile for ferrous sulfate was 35% for 1st hour, 45-75% for 2nd hour and 60-85% for third hour and not less than 85% for 4th hour. The release rate controlling polymer used was various concentrations of Methoccel K15M CR with different concentrations of Microcrystalline cellulose (Avicel PH 101). The maximum release percentage of Ferrous Sulphate was obtained from 2.5 % of Methocel K15M CR and 30 % Avicel PH 101 containing pellets (F-4) and it was 92.32%. And the minimum release percentage of Ferrous Sulphate was obtained from 10 % of Methocel K15M CR and 35.7% Avicel PH 101 containing pellets (F-1) and it was 86.36%. The release profile from other formulations containing 35.4% Methocel K 15M CR & 7.5% Avicel (F-2) and 32% Methocel K 15M CR & 4% Avicel (F-3) were also within desired range. The effect of Eudragit coating (enteric) and the presence of PEG and HPMC in the film coating composition on the drug release were also investigated. Hydrophobic matrix pellets prepared using lower concentrations of Methocel K15M CR were found to be best suited for modulating the delivery of the ferrous sulphate from the combination. Key words: Non Pariel Seeds (NPS); Pan Coater; Ascorbic acid; Methocel K15M CR; Pelletization; PEG; Avicel PH 101; Xanthan gum.DOI: 10.3329/sjps.v2i2.5824Stamford Journal of Pharmaceutical Sciences Vol.2(2) 2009: 53-58

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Evaluation of the Release of Ascorbic Acid in Prolonged-Release Tablets by in vitro Dissolution Tests

International Journal of Pharmaceutical Sciences and Drug Research ◽

10.25004/ijpsdr.2018.100415 ◽

2018 ◽

Vol 10 (4) ◽

Author(s):

E.Damasceno Junior ◽

J. M. F. DE Almeida ◽

I. N. Silva ◽

M. S. B. Silva ◽

N. S. Fernandes

Keyword(s):

Ascorbic Acid ◽

Absorption Spectroscopy ◽

Release Kinetics ◽

In Vitro Dissolution ◽

Prolonged Release ◽

Molecular Absorption ◽

Dissolution Medium ◽

Dissolution Tests ◽

Molecular Absorption Spectroscopy

In vitro dissolution tests are an extremely important tool in the development and quality control of drugs, making it possible to evaluate the performance or efficiency of the pharmaceutical form in releasing the active substance through the amount dissolved in the dissolution medium when the product is subjected to specific equipment. In this sense, the main objective of the present study was to evaluate the release of ascorbic acid in prolonged release commercial vitamin C tablets by dissolution tests. Ascorbic acid and drugs of two different brands were characterized using the techniques of Molecular Absorption Spectroscopy in the Region of Infrared (IR), Thermogravimetry/Derived Thermogravimetry (TG/DTG) and Differential Scanning Calorimetry (DSC). The in vitro dissolution tests were performed in a dissolver with a paddle apparatus at a temperature of 37°C (± 0.5°C), employing 900 mL of ultrapure water as the dissolution medium and a stirring speed of 50 rpm. The ascorbic acid dissolved in the aliquots of dissolution media obtained during the tests were quantified using the UV-Vis Molecular Absorption Spectroscopy technique. From the dissolution profiles, it was observed that the formulations of both brands promoted a prolonged release of ascorbic acid. The brand drug A dissolved about 67% of the active principle in about 360 minutes. The brand drug B, however, dissolved about 72% at the same dissolution time. Release kinetics was evaluated using kinetic models such as order zero, first order and Higuchi. The model that best fit the experimental data was that of Higuchi.

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Formulation of Quaternized Aminated Chitosan Nanoparticles for Efficient Encapsulation and Slow Release of Curcumin

Molecules ◽

10.3390/molecules26020449 ◽

2021 ◽

Vol 26 (2) ◽

pp. 449

Author(s):

Ahmed M. Omer ◽

Zyta M. Ziora ◽

Tamer M. Tamer ◽

Randa E. Khalifa ◽

Mohamed A. Hassan ◽

...

Keyword(s):

Slow Release ◽

Sodium Tripolyphosphate ◽

Chitosan Nanoparticles ◽

Gastric Fluid ◽

Release Profile ◽

Simulated Gastric Fluid ◽

Maximum Value ◽

Structure Surface ◽

Drug Encapsulation Efficiency

An effective drug nanocarrier was developed on the basis of a quaternized aminated chitosan (Q-AmCs) derivative for the efficient encapsulation and slow release of the curcumin (Cur)-drug. A simple ionic gelation method was conducted to formulate Q-AmCs nanoparticles (NPs), using different ratios of sodium tripolyphosphate (TPP) as an ionic crosslinker. Various characterization tools were employed to investigate the structure, surface morphology, and thermal properties of the formulated nanoparticles. The formulated Q-AmCs NPs displayed a smaller particle size of 162 ± 9.10 nm, and higher surface positive charges, with a maximum potential of +48.3 mV, compared to native aminated chitosan (AmCs) NPs (231 ± 7.14 nm, +32.8 mV). The Cur-drug encapsulation efficiency was greatly improved and reached a maximum value of 94.4 ± 0.91%, compared to 75.0 ± 1.13% for AmCs NPs. Moreover, the in vitro Cur-release profile was investigated under the conditions of simulated gastric fluid [SGF; pH 1.2] and simulated colon fluid [SCF; pH 7.4]. For Q-AmCs NPs, the Cur-release rate was meaningfully decreased, and recorded a cumulative release value of 54.0% at pH 7.4, compared to 73.0% for AmCs NPs. The formulated nanoparticles exhibited acceptable biocompatibility and biodegradability. These findings emphasize that Q-AmCs NPs have an outstanding potential for the delivery and slow release of anticancer drugs.

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Decreased Platelet Vitamin C in Diabetes Mellitus; Possible Role in Peraggregatoon

10.1055/s-0039-1687640 ◽

1979 ◽

Author(s):

K.E. Sarji ◽

J. Gonzalez ◽

H. Hempling ◽

J.A. Colwell

Keyword(s):

Ascorbic Acid ◽

Arachidonic Acid ◽

Platelet Aggregation ◽

Vitamin C ◽

Platelet Rich Plasma ◽

Solution Ph ◽

Dose Dependent Fashion ◽

Insulin Dependent Diabetic ◽

Induced Aggregation

To determine whether Vitamin C might relate to the increased platelet sensitivity in the diabetic, we have measured levels of platelet Vitamin C and studied the effects of Vitamin C on platelet aggregation. Ascorbic acid levels in washed platelets from diabetics were significantly lower than from normals (4s.2±3 μg/1010 platelets vs. 2s.s±2 μg/1010 platelets, p<.001). The effects of ascorbic acid on platelet aggregation in vitro were studied by adding ascorbic acid in buffered solution (pH 7.35) prior to-aggregating agents. Ascorbic acid in platelet-rich plasma consistently inhibited platelet aggregation with threshold concentrations of ADP, epinephrine, and collagen. With washed platelets, ascorbic acid inhibited arachidonic, acid-induced aggregation. When platelets were incubated at 37°C for 10 minutes with varying concentrations of ascorbic acid, rewashed, and aggregation with arachidonic acid tested, aggregation was inhibited in a linear dose-dependent fashion. Oral ingestion of ascorbic acid (2 gm/day) for seven days by normal non-smoking males produced a marked inhibition of aggregation. In a similar study, platelets from an insulin-dependent diabetic showed no change in aggregation. These results suggest that platelet levels of ascorbic acid may relate to the hyperaggregat ion of platelets from diabetics.

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Assessment of physical and dissolution characteristics of various itraconazole capsule formulations: a comparative analysis

International Journal of Research in Dermatology ◽

10.18203/issn.2455-4529.intjresdermatol20194665 ◽

2019 ◽

Vol 5 (4) ◽

pp. 765

Author(s):

Rajan Verma ◽

Shrikant Hodge ◽

Chandrashekhar Gargote ◽

Prakash Modi ◽

Naresh Upreti ◽

...

Keyword(s):

Size Distribution ◽

Phosphate Buffer ◽

Acetate Buffer ◽

Simulated Gastric Fluid ◽

Physical Parameters ◽

Dissolution Profile ◽

Lauryl Sulfate ◽

Complete Dissolution ◽

Innovator Product

Background: This in vitro study compared physical parameters and the dissolution profile of innovator itraconazole capsule formulation, i-Tyza, and 5 other generic capsule formulations available in the Indian market.Methods: The number of pellets and size distribution were determined using naked eye examination and sieving method, respectively. Dissolution profile of formulations was done at 15, 30, 45, and 60 minutes, using a United States Pharmacopeia type II Paddle apparatus in simulated gastric fluid (SGF, pH 1.2) without enzymes, acetate buffer (pH 4.5) with 0.5% sodium lauryl sulfate (SLS), and phosphate buffer (pH 6.8) with 0.5% SLS.Results: All formulations had capsule size 0. Capsule fill weight (~335 to ~510 mg) and total pellet number (127 to 810) varied across formulation, with the innovator brand having the highest number of pellets. Innovator product and i-Tyza had similar fill weight (~460 mg). Pellet size distribution of the innovator product, brand 2, brand 3, and i-Tyza was relatively narrow. In SGF, except brand 1 (84% dissolved) and brand 5 (80% dissolved), all the formulations had near-complete (>85% drug dissolved) or complete dissolution (>90% drug dissolved) at 60 minutes. In acetate buffer, pH 4.5 with 0.5% SLS and phosphate buffer, pH 6.8 with 0.5% SLS, only the innovator product and i-Tyza demonstrated near-complete to complete dissolution at 60 minutes (96% and 90% dissolved).Conclusions: Across all the itraconazole generic formulations evaluated, i-Tyza had comparable physical characteristics and dissolution profile to the innovator product. The in vitro dissolution profile of i-Tyza may indicate adequate in vivo performance.

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Development of a reservoir type prolonged release system with felodipine via simplex methodology

Medicine and Pharmacy Reports ◽

10.15386/cjmed-526 ◽

2015 ◽

Vol 89 (1) ◽

pp. 128-136

Author(s):

Rareș Iuliu Iovanov ◽

Ioan Tomuță ◽

Sorin Emilian Leucuța

Keyword(s):

Simplex Method ◽

Release Kinetics ◽

Prolonged Release ◽

Lauryl Sulfate ◽

Pore Former ◽

Release System ◽

Reservoir Type ◽

Model Drug ◽

Kinetics Of

Background and aims. Felodipine is a dihydropyridine calcium antagonist that presents good characteristics to be formulated as prolonged release preparations. The aim of the study was the formulation and in vitro characterization of a reservoir type prolonged release system with felodipine, over a 12 hours period using the Simplex method.Methods. The first step of the Simplex method was to study the influence of the granules coating method on the felodipine release. Furthermore the influence of the coating polymer type, the percent of the coating polymer and the percent of pore forming agent in the coating on the felodipine release were studied. Afterwards these two steps of the experimental design the percent of Surelease applied on the felodipine loaded granules and the percent of pore former in the polymeric coating formulation variables were studied. The in vitro dissolution of model drug was performed in phosphate buffer solution (pH 6.5) with 1% sodium lauryl sulfate. The released drug quantification was done using an HPLC method. The release kinetics of felodipine from the final granules was assessed using different mathematical models.Results. A 12 hours release was achieved using granules with the size between 315 – 500 µm coated with 45% Surelease with different pore former ratios in the coating via the top-spray method.Conclusion. We have prepared prolonged release coated granules with felodipine using a fluid bed system based on the Simplex method. The API from the studied final formulations was released over a 12 hours period and the release kinetics of the model drug substance from the optimized preparations fitted best the Higuchi and Peppas kinetic models.

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FORMULATION AND EVALUATION OF SUSTAINED RELEASE MATRIX TABLET OF LORNOXICAM BY DIRECT COMPRESSION METHOD

Journal of Pharmaceutical and Scientific Innovation ◽

10.7897/2277-4572.105218 ◽

2021 ◽

Vol 10 (5) ◽

pp. 131-136

Author(s):

Asim pasha ◽

C N Somashekhar

Keyword(s):

Drug Release ◽

Sustained Release ◽

Matrix Tablets ◽

In Vitro Dissolution ◽

Prolonged Release ◽

Matrix Tablet ◽

Direct Compression ◽

Dissolution Profile ◽

Drug Content

The aim of the present work was to develop sustained release Lornoxicam matrix tablets with polymers like HPMC K15M, Ethyl cellulose, and Crospovidone as carriers in varying quantities. Direct compression was used to make matrix tablets. Various assessment parameters, such as hardness, friability, thickness, percent drug content, weight variation, and so on, were applied to the prepared formulations. In vitro dissolution studies were carried out for 24 hrs. The tablets were subjected to in-vitro drug release in (pH 1.2) for first 2 hrs. Then followed by (pH 6.8) phosphate buffer for next 22 hrs. And the results showed that among the six formulations FL3 showed good dissolution profile to control the drug release respectively. The drug and polymer compatibility were tested using FT-IR spectroscopy, which revealed that the drug was compatible with all polymers. It is also required to design an appropriate prolonged release formulation for Lornoxicam in order to maintain the drug's release. Hence by using the compatible polymers sustained release tablets were formulated and subjected for various types of evaluation parameters like friability, hardness, drug content and dissolution behaviour. Finally, the findings reveal that the prepared sustained release matrix tablets of lornoxicam have improved efficacy and patient compliance.

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Crushed Tablets: Does the Administration of Food Vehicles and Thickened Fluids to Aid Medication Swallowing Alter Drug Release?

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j39w3v ◽

2014 ◽

Vol 17 (2) ◽

pp. 207 ◽

Cited By ~ 26

Author(s):

Yady Juliana Manrique-Torres ◽

Danielle J Lee ◽

Faiza Islam ◽

Lisa M Nissen ◽

Julie A.Y. Cichero ◽

...

Keyword(s):

Drug Release ◽

Orange Juice ◽

Immediate Release ◽

Drug Dissolution ◽

In Vitro Dissolution ◽

Simulated Gastric Fluid ◽

Drug Bioavailability ◽

Thickening Agents

Purpose. To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. Methods. Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. Results. Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. Conclusions. Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their potential to influence therapeutic outcomes is warranted. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Dietary regulation of intestinal ascorbate uptake in guinea pigs

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1991.260.1.g108 ◽

1991 ◽

Vol 260 (1) ◽

pp. G108-G118 ◽

Cited By ~ 3

Author(s):

W. H. Karasov ◽

B. W. Darken ◽

M. C. Bottum

Keyword(s):

Ascorbic Acid ◽

Vitamin C ◽

Brush Border ◽

Guinea Pigs ◽

Dietary Regulation ◽

Intestinal Brush Border ◽

Pregnancy And Lactation ◽

Human Adults ◽

Ascorbate Uptake

We measured ascorbic acid (AA) uptake across the intestinal brush border in vitro in intact tissue from guinea pigs fed maintenance AA (200 mg/kg diet) or made hypervitaminotic (5,000 mg/kg diet) or hypovitaminotic (chronically and acutely). Total uptake per centimeter ileum was 25-50% lower in hypervitaminotic juvenile, adult male, and lactating guinea pigs compared with their respective controls, whereas carrier-mediated D-glucose uptake and Na(+)-independent AA uptake were similar. High dietary ascorbate specifically reduced the Vmax for carrier-mediated AA uptake. Hypovitaminosis had no significant effect on uptake of AA or other solutes. We performed diet-switching experiments (high-AA diet to maintenance diet) with young and adult guinea pigs to determine the reversibility of the downregulation. In adult guinea pigs, the downregulation of AA uptake was reversible within 7 days. In the young of mothers fed high AA during pregnancy and lactation, and which fed on high AA for 14 days after weaning, the downregulation was reversible within 14 days. Thus regulation of AA uptake is reversible and therefore probably does not play a significant role in the development of vitamin C dependency in human adults, or their young, after ingestion of megadoses of ascorbic acid.

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