Optimizing a wet granulation process to obtain high-dose sustained-release tablets with Compritol 888 ATO

Abstract Background: Methamphetamine (METH) and amphetamine (AMP) concentrations in 200 plasma and 590 oral fluid specimens were used to evaluate METH pharmacokinetics and pharmacodynamics after oral administration of sustained-release METH. Methods: Eight participants received four oral 10-mg S-(+)-METH hydrochloride sustained-release tablets within 7 days. Three weeks later, five participants received four oral 20-mg doses. Blood samples were collected for up to 24 h and oral fluid for up to 72 h after drug administration. Results: After the first oral dose, initial plasma METH detection was within 0.25–2 h; cmax was 14.5–33.8 μg/L (10 mg) and 26.2–44.3 μg/L (20 mg) within 2–12 h. In oral fluid, METH was detected as early as 0.08–2 h; cmax was 24.7–312.2 μg/L (10 mg) and 75.3–321.7 μg/L (20 mg) and occurred at 2–12 h. The median oral fluid-plasma METH concentration ratio was 2.0 across 24 h and was highly variable. Neutral cotton swab collection yielded significantly higher METH and AMP concentrations than citric acid candy-stimulated expectoration. Mean (SD) areas under the curve for AMP were 21% ± 25% and 24% ± 11% of those observed for METH in plasma and oral fluid, respectively. After a single low or high dose, plasma METH was >2.5 μg/L for up to 24 h in 9 of 12 individuals (mean, 7.3 ± 5.5 μg/L at 24 h); in oral fluid the detection window was at least 24 h (mean, 18.8 ± 18.0 μg/L at 24 h). The plasma and oral fluid 24-h METH detection rates were 54% and 60%, respectively. After four administrations, METH was measurable for 36–72 h (mean, 58.3 ± 14.5 h). Conclusions: Perceived advantages of oral fluid for verifying METH exposure compared with urine include simpler specimen collection and reduced potential for adulteration, but urine offers higher analyte concentrations and a greater window of detection.

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Formulation and In Vitro Evaluation of Bilayer Tablets of Lansoprazole and Amoxycillin Trihydrate for the Treatment of Peptic Ulcer

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v11i1.4481 ◽

2021 ◽

Vol 11 (1) ◽

pp. 23-31

Author(s):

Neha Singh ◽

Durga Pandey ◽

Nilesh Jain ◽

Surendra Jain

Keyword(s):

Sustained Release ◽

Immediate Release ◽

Flow Property ◽

Wet Granulation ◽

Formulation Development ◽

In Vitro Evaluation ◽

Bilayer Tablets ◽

Bilayer Tablet ◽

Sustained Release Tablets

The present work involves the formulation development, optimization and In-vitro evaluation of bilayer tablet containing Lansoprazole in the immediate release layer and Amoxycillin in the sustained release layer, using sodium starch glycolate as a super disintegrant for the immediate release layer and the hydrophilic matrix HPMC K100M, hydrophobic matrix Ethyl cellulose are used in the sustained release layer. Bilayer tablet showed as initial burst effect to provide dose of immediate release layer Lansoprazole to control the acid secretion level and the sustained release of Amoxycillin for 24 hours. Immediate and sustained release tablets were formulated by wet granulation method because of the poor flow property of the blends. The prepared bilayer tablet was evaluated for their precompression parameters, physical characteristics like hardness, friability, uniformity of weight, uniformity of drug content, swelling index, In-vitro floating studies and In-vitro drug release. The release of the lansoprazole from the immediate release layer was found to be 97.46 ± 0.15% in 15minutes. The release of Amoxycillin Trihydrate for the sustained release floating layer was found to be 98.25 ± 0.14% in 12 hours. Lansoprazole potentiate the effect of Amoxycillin. Hence the bilayer tablets of Lansoprazole and Amoxycillin were used to improve patient compliance towards the effective management of ulcer. Keywords: bilayer tablet, Lansoprazole, and Amoxycillin, sustained release

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Product of Modified Rice Starch (Era-Gel®) and its Utilization in Pharmaceutical Industry

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.93-94.675 ◽

2010 ◽

Vol 93-94 ◽

pp. 675-678

Author(s):

Varatus Vongsurakrai ◽

Saiyavit Varavinit

Keyword(s):

Powder Mixture ◽

Corn Starch ◽

Rice Starch ◽

Wet Granulation ◽

High Dose ◽

Granulation Process ◽

Tablet Press ◽

Starch Paste ◽

Single Material ◽

Potential Use

Pregelatinized rice starch (Era-Gel ® ) was prepared by physical modification. The degree of pregelatinization was controlled to an appropriate level. With the addition of small amount of pregelatinized rice starch , a slightly sticky, damped mass was obtained. Pregelatinized rice starch was tested for a potential use as a tablet filler or binder in wet granulation process. Two hydrochlorothiazide formulations were compared. One formulation comprised HCTZ and PRS; the powder mixture was damped with water. The other formulation contained HCTZ, lactose as filter, corn starch as binder and also as tablet disintegrant. In the later case, the powder mixture was damped with starch paste. Both granulations were compressed on an instrumented tablet press. The tablets were evaluated for their hardness, friability, disintegration, and also dissolution. The results indicated that both formulations were comparable in all aspects. It dissolution was found to exceed the USP requirement. It was demonstrated that three components, i.e. , lactose, corn starch paste, and disintegrant could be replaced with only one single material, PRS. It was also found that PRS could perform well in acetaminophen tablet formulation which was a high-dose drug and tended to cap; however, small amount of extra binder and disintegrant were needed. It could be seen that PRS had a great potential use in wet granulation process.

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Design and Development of Prochlorperazine Maleate Sustained Release Tablets: Influence of Hydrophilic Polymers on the Release rate and In vitro Evaluation

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2010.3.2.10 ◽

2010 ◽

Vol 3 (2) ◽

pp. 965-977

Author(s):

Nagasamy Venkatesh D ◽

Sankar S ◽

S N Meyyanathan ◽

K Elango ◽

B Suresh ◽

...

Keyword(s):

Drug Release ◽

Sustained Release ◽

Release Kinetics ◽

Methyl Cellulose ◽

Matrix Tablets ◽

In Vitro Dissolution ◽

Wet Granulation ◽

Sustained Release Tablets ◽

Compression Characteristics

The objective of the present investigation was to develop and evaluate sustained release matrix tablets of prochlorperazine maleate employing different types and levels of hydrophilic matrix agents namely hydroxyl propyl methyl cellulose (HPMC), carbopol and combination of these polymers by wet granulation technique. Prior to compression process, the prepared granules were evaluated for its flow and compression characteristics. The in vitro dissolution of the newly formulated sustained release tablets were compared with standard formulation. The excipients used in this study did not alter the physicochemical properties of the drug, as indicated by the thermal analysis using differential scanning calorimetry technique. The flow and compression characteristics of the prepared granules significantly improved by virtue of granulation process. Also, the prepared matrix tablets showed good mechanical properties in terms of hardness and friability. HPMC based tablet formulations alone showed high release retarding efficiency as compared to carbopol, carbopol and HPMC combinations. The studies indicated that the drug release can be modulated by varying concentrations of polymers. Mathematical analysis of the release kinetics indicated the nature of the drug release from the matrix tablets followed quasi-fickian obeying first order kinetics.

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Development and Characterization of Bilayer Sustained Release Tablets of Tramadol HCl and Acetaminophen

Global Pharmaceutical Sciences Review ◽

10.31703/gpsr.2016(i-i).02 ◽

2016 ◽

Vol I (I) ◽

pp. 6-16

Author(s):

Rashid Javed ◽

Sana Ijaz ◽

Kainat Waqar ◽

Muhammad Imran Khan

Keyword(s):

Sustained Release ◽

Promising Result ◽

Methyl Cellulose ◽

Matrix Tablets ◽

Wet Granulation ◽

Tramadol Hydrochloride ◽

Weight Variation ◽

Sustained Release Tablets ◽

S 100 ◽

Eudragit S 100

The aim of the present study was to develop bilayer sustained release tablets of to improve patient compliance of two drugs, tramadol and paracetamol. Immediate release layer contained both drugs tramadol hydrochloride and acetaminophen while the sustained release layer was designed only for the tramadol hydrochloride. Hydrophobic polymers Eudragit L-100, Eudragit S-100 and hydrophilic polymer hydroxy propyl methyl cellulose (HPMC K15), and wet granulation technique to produce bilayer matrix tablets. FTIR studies revealed no incompatibility among the ingredients. Out of 16 trials developed and characterized for weight variation, thickness, diameter, hardness, and friability, F16 showed promising result with immediate layer releasing drug 29% in 2 hours followed by sustained release 77% drug over 12 hours and followed zero order release. Therefore, bilayer sustained release tablets of tramadol with simultaneous loading of Paracetamol can be developed using Eudragit S-100 and hydroxyl propyl methylcellulose (HPMC K15) at equimolar content levels.

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Preparation and Characterization of a Gastric Floating Dosage Form of Capecitabine

BioMed Research International ◽

10.1155/2013/495319 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Ehsan Taghizadeh Davoudi ◽

Mohamed Ibrahim Noordin ◽

Ali Kadivar ◽

Behnam Kamalidehghan ◽

Abdoreza Soleimani Farjam ◽

...

Keyword(s):

Sustained Release ◽

Sodium Bicarbonate ◽

Hydroxypropyl Methylcellulose ◽

Lag Time ◽

Wet Granulation ◽

Sustained Release Tablets ◽

Floating Tablet ◽

The Stability ◽

The Right

Gastrointestinal disturbances, such as nausea and vomiting, are considered amongst the main adverse effects associated with oral anticancer drugs due to their fast release in the gastrointestinal tract (GIT). Sustained release formulations with proper release profiles can overcome some side effects of conventional formulations. The current study was designed to prepare sustained release tablets of Capecitabine, which is approved by the Food and Drug Administration (FDA) for the treatment of advanced breast cancer, using hydroxypropyl methylcellulose (HPMC), carbomer934P, sodium alginate, and sodium bicarbonate. Tablets were prepared using the wet granulation method and characterized such that floating lag time, total floating time, hardness, friability, drug content, weight uniformity, andin vitrodrug release were investigated. The sustained release tablets showed good hardness and passed the friability test. The tablets’ floating lag time was determined to be 30–200 seconds, and it floated more than 24 hours and released the drug for 24 hours. Then, the stability test was done and compared with the initial samples. In conclusion, by adjusting the right ratios of the excipients including release-retarding gel-forming polymers like HPMC K4M, Na alginate, carbomer934P, and sodium bicarbonate, sustained release Capecitabine floating tablet was formulated.

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Formulation Development and In-vitro Evaluation of Sustained Release Tablets of Metoprolol Succinate

Research Journal of Pharmaceutical Dosage Forms and Technology ◽

10.52711/0975-4377.2021.00044 ◽

2021 ◽

pp. 269-275

Author(s):

Priyanka M. Salve ◽

Rajendra K. Surawase

Keyword(s):

Sustained Release ◽

Half Life ◽

Wet Granulation ◽

Direct Compression ◽

Formulation Development ◽

Metoprolol Succinate ◽

Dissolution Studies ◽

Weight Variation ◽

Sustained Release Tablets

Metoprolol succinate is a β1 selective antagonist used an anti-arrhythmic, antiagina, antihypertensive. sustained release tablet of metoprolol succinate were formulated using polymers. The half-life of drug is relatively 4-6 hours. The formulation of metoprolol succinate tablet were produced by direct compression or wet granulation method. The formulations were evaluated for thickness, hardness, weight variation, friability and dissolution, drug content all the physical characteristics of the formulated tablets were within acceptable limits. The dissolution studies of Metoprolol succinate sustained release tablets reflects USP specification NMT 25%by 1 hours, 20-40%by 4 hours,40-60%by 8 hours and more than 80% by 20 hrs.

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FORMULATION AND EVALUATION OF LEVOFLOXACIN HEMIHYDRATE SUSTAINED RELEASE TABLET FROM HYDROPHILIC MATRICES

INDIAN DRUGS ◽

10.53879/id.49.01.p0043 ◽

2012 ◽

Vol 49 (01) ◽

pp. 43-49

Author(s):

S. K Sahoo ◽

◽

A Behera ◽

S. Patil

Keyword(s):

Drug Release ◽

Sustained Release ◽

Methyl Cellulose ◽

Wet Granulation ◽

Drug Diffusion ◽

Weight Variation ◽

Lower Viscosity ◽

Sustained Release Tablets ◽

Through Diffusion ◽

Higuchi Model

Stable sustained release tablets of levofloxacin hemihydrate were successfully prepared by wet granulation technique. Compatible excipients were selected and different formulations were prepared with varying proportion and grades of hydroxy propyl methyl cellulose. Tablets were prepared by compressing free flowing granules and evaluated for hardness, thickness, friability, weight variation, percentage drug content and drug release. As concentration of HPMC increased the drug release decreased might be due to increased amount of polymer around tablets provided gelation which inhibits the release. For formulation F5 only 55 % drug was released in 8 h whereas up to 90 % drug was release for formulation F2 and F3 within the same time. Thus, higher viscosity HPMC retards the drug release directly than lower viscosity HPMC. All the formulations follow Higuchi model which has indicated that drug release from homogenous matrix was through diffusion. Thus, increase in concentration of polymer decreases the drug diffusion from tablet.

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