Effervescent Mixture Research Articles

Formulation and optimization of olanzapine-carboxylic acid cocrystals orodispersible tablets: In-vitro/ In-vivo study

Oromucosal delivery of olanzapine (OLZ) is an optimal strategy to overcome low oral bioavailability as well as improve medication adherence. However, its poor aqueous solubility may hinder its absorption through the buccal mucosa. The aim of the study is to enhance OLZ solubility and dissolution via cocrystal formation, followed by incorporation into an orodispersible tablet (ODT) based on an effervescent mixture and crospovidone as a superdisintegrant mixture. OLZ was cocrystallized with different carboxylic acids using slow solvent evaporation, and the optimal cocrystal formula was subjected to solid state characterization. Central composite design (CCD) was used in the modeling and optimization of the ODT independent variables (amounts of crospovidone and effervescent mixture). The optimized OLZ cocrystal ODTs were subjected to microenvironmental pH, stability, and in-vivo studies. The results revealed that the OLZ:itaconic acid at 1:1 M ratio showed a 7.86 fold increase in OLZ solubility and 86.71 ± 1.07 % dissolution efficiency (DE60 %) with FTIR, XRPD, and DSC diffractograms that confirmed the cocrystal formation. The optimized OLZ cocrystal ODTs exhibited hardness of 3.6 ± 0.1 kg/cm2, disintegration time of 11.66 ± 1.52 s, wetting time of 36.33 ± 2.51 s, and 94.26 ± 2.77 % OLZ released within 15 min with a DE60 % of 91.65 ± 0.98 %. Finally, the optimized OLZ cocrystal ODTs showed a significant (p < 0.01) higher Cmax and AUC with a relative bioavailability of 139.08 % compared to the Schisolazine©10 mg ODTs. These results suggest that OLZ:itaconic acid cocrystal incorporated into an ODT containing a superdisintegrant mixture of effervescence mixture and crospovidone is a potential approach for enhancement of oromucosal delivery of OLZ.

FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLET OF PROCHLORPERAZINE MALEATE

In the present work, fast disintegrating tablets of prochlorperazine maleate were designed with a view to enhance patient compliance by effervescent method. Prochlorperazine Maleate, a potent antipsychotic medication with antiemetic properties, holds significance in treating various conditions such as nausea, vomiting, and vertigo. The decision to formulate it into orodispersible tablets aimed to address issues related to patient compliance and convenience, particularly for individuals who experience difficulty swallowing conventional tablets. Formulation F10, enriched with 10% Croscarmellose sodium as a superdisintegrant and an effervescent mixture for taste masking, exhibited remarkable characteristics. Croscarmellose sodium, chosen for its exceptional disintegration properties, ensures rapid breakdown upon contact with saliva, facilitating swift drug release and subsequent onset of action. Moreover, the incorporation of an effervescent mixture not only aids in masking the potentially unpleasant taste of Prochlorperazine Maleate but also holds the potential to enhance palatability and overall patient acceptance. Physicochemical characterization of Prochlorperazine Maleate unveiled favorable attributes, including a loss on drying of 0.413±0.002%, a melting point range of 234-236°C, and a moisture content of 0.0354%, affirming its suitability for formulation into orodispersible tablets. Through dissolution profile comparisons, formulation F10 demonstrated superior drug release kinetics compared to the commercial formulation, underscoring its potential therapeutic advantages.

EFFECT OF EFFERVESCENCE IN COMBINATION WITH SUPERDISINTEGRANTS IN THE FORMULATION OF PROPRANOLOL HCL ORAL DISINTEGRATING TABLETS

ABSTRACTObjective: The current research work is intended to formulate propranolol HCl (PLH) as orally disintegrating tablet (ODT). It is also intending to checkthe superiority in a combination of superdisintegrants and effervescent mixture than the use of superdisintegrants alone by a direct compressiontechnique. To fasten the onset of action and thereby enhancing the bioavailability of PLH in comparison to its conventional tablets.Methods: Standard calibration curve of PLH was obtained in pH 6.8 phosphate buffer by spectrophotometric method, drug-excipient compatibilitystudies were carried by Fourier transform infrared (FT-IR) studies. All the formulations were evaluated for pre and postcompression studies.Accelerated stability studies were carried out up to 6 months for the optimized formulation, EF3.Results and Discussion: Superdisintegrants used in the study are compatible with PLH. Pre- and post-compression parameters were within theacceptable limits for all formulations. In vitro dissolution kinetic studies indicate the release of PLH from ODT increases as the concentration ofsuperdisintegrants as well as the ratio of citric acid: NaHCO3 of effervescent mixture increases. Formulations with an effervescent mixture are havingrapid disintegration and dissolution rate when compared to the formulations with superdisintegrants alone. The order of superdisintegrants inenhancing the dissolution rate of PLH is crospovidone (CPV) &gt; croscarmellose sodium (CCS) &gt; sodium starch glycolate (SSG). Formulation, EF3 (10%CPV and 1:3, citric acid: NaHCO3 ratio, respectively) had the highest dissolution efficiency at 10 minutes (DE10=82.74%); the first order dissolutionrate constant (K1=0.141/minutes) with a regression coefficient (r2=0.974) and lesser time for 90% of drug release (t90=4 minutes), was considered asthe optimal ODT in this study. Formulation EF3, passed the test for stability.Conclusion: Hence, an effective PLH ODT was formulated by the direct compression technique with disintegration by combination of superdisintegrantsand effervescent mixture, will fasten the onset of action and enhances the bioavailability of PLH in comparison to its conventional tablets.Keywords: Propranolol HCl, Orally disintegrating tablet, Sodium starch glycolate, Croscarmellose sodium, Crospovidone, Direct compression, In vitrodissolution studies.

Formulation and Pharmacokinetics of Ketorolac Tromethamine Floating Compression Coated Mini-Tablets

Present research is intended to develop the Ketorolac Tromethamine (KTM) effervescent floating mini-tablets using compression coating method. Mini-tablets have the advantages of both tablets and multiparticulate formulations such as pellets. The main principle of floating mini-tablets can be applied to decrease the irritant effect of KTM on the stomach by avoiding the direct contact with the gastric mucosa and obtaining a low dosage for prolonged periods. KTM mini-tablets were prepared using 4 mm round flat punches and compression coated with hydroxypropyl methylcellulose and effervescent mixture. The prepared tablets were evaluated for weight variation, thickness, friability, hardness, drug content, in vitro buoyancy and in vitro release and the best formulation was subjected to further in vivo examination. The prepared mini-tablets exhibited satisfactory physicochemical characteristics. Formulation F3 offered the best controlled drug release (99.46 ± 0.93% in 12 h and T80%=9.4 h) along with floating lag time 12 h. Pharmacokinetic studies of F3 formulation in male albino rabbits showed 2.25-fold higher bioavailability and 1.35-fold higher Cmax compared to immediate release core mini-tablets. Hence development of KTM effervescent compression-coated floating mini-tablets is the best way to give through oral route to maximize the therapy.

Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride.

PurposeThe aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form.Materials and methodsSustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release.ResultsIn vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031). The pharmacokinetic results indicated that the area under the curve (AUC0–∞) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton®) and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022).ConclusionThe prepared floating tablets of ITO HCl (F10) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

Solid effervescent formulations as new approach for topical minoxidil delivery

Currently marketed minoxidil formulations present inconveniences that range from a grease hard aspect they leave on the hair to more serious adverse reactions as scalp dryness and irritation. In this paper we propose a novel approach for minoxidil sulphate (MXS) delivery based on a solid effervescent formulation. The aim was to investigate whether the particle mechanical movement triggered by effervescence would lead to higher follicle accumulation. Preformulation studies using thermal, spectroscopic and morphological analysis demonstrated the compatibility between effervescent salts and the drug. The effervescent formulation demonstrated a 2.7-fold increase on MXS accumulation into hair follicles casts compared to the MXS solution (22.0±9.7μg/cm2 versus 8.3±4.0μg/cm2) and a significant drug increase (around 4-fold) in remaining skin (97.1±29.2μg/cm2) compared to the drug solution (23.5±6.1μg/cm2). The effervescent formulations demonstrated a prominent increase of drug permeation highly dependent on the effervescent mixture concentration in the formulation, confirming the hypothesis of effervescent reaction favoring drug penetration. Clinically, therapy effectiveness could be improved, increasing the administration interval, hence, patient compliance. More studies to investigate the follicular targeting potential and safety of new formulations are needed.

IN VITRO AND IN VIVO EVALUATION OF THE GASTRORETENTIVE FLOATING DOSAGE FORM

The aim of the present investigation was to develop and optimize gastro retentive floating system of Pantoprazole f or the efficient treatment of acid related disorders and H. Pylori infections. Floating tablets were developed using central composite design (CCD), and optimization was done by employing resp onse surface methodology . The floating tablets were prepared wit h HPMC K 4 M/Ethyl cellulose and natural seed polymer of Delonix regia by wet granulation technique. Buoyancy was achieved by adding an effervescent mixture of sodium bicarbonate and anhydrous citric acid. The Optim ized formulation (BS 3 ) showed no significan t change in physical appearance, drug content, total buoyancy time, or in vitro dissolution pattern after storage at 40°C/75 % relative humidity for 1 month. The best formulation was selected based on in vitro characteristics and was used for the in vivo r adiographi c studies by incorporating BaSO 4 . Evaluation of Gastric retention using x - Ray imaging studies were performed on rabbit to justify the increased gastric residence time of the dosage form in the stomach, based on the floating principle. Further the floating tablets were evaluated for its antiulcer activity in Male wristar rats by ethanol induced ulcer in comparison with standard. The floating formulation shows excellent buoyancy and better gastric cytoprotection when compare d with standard drug.

Effervescent tablet formulation for enhanced patient compliance and the therapeutic effect of risperidone

Risperidone is a poorly water soluble atypical antipsychotic drug. This work investigated the potential of developing risperidone effervescent tablets to facilitate drug administration and mask drug taste. The solid dispersion technique was selected to improve drug solubility due to its ease of scaling up, reproducibility and affordable cost. Thirty formulas were prepared adopting a 51.21.31 full factorial design. Trehalose, Inulin, pregelatinized starch, carboxymethylcellulose sodium and Eudragit E100 were used as hydrophilic carriers at different ratios. Rotovap, lyophilization and the kneading-oven were applied as solvent evaporation techniques. Differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy showed that the drug was present as amorphous material entrapped within the carrier matrix. Eight tablet blends were prepared using different effervescent mixture ratios with or without binder and lubricant/glidant mixture. All of the blends had acceptable flowability, acceptable effervescence times and immediate drug release that could not be achieved by any of the control formulas. The formula of choice contained 40% effervescent mixture, 5% starch, 1% boric acid, 1% aspartame and sufficient lactose. The relative bioavailability (RB) of risperidone from this formula was 161.41% with a significantly higher extent of absorption compared to the market conventional tablets. This formula may be promising in improving patient compliance and drug efficiency.

Development and physical evaluation of Maytenus ilicifolia effervescent granules using factorial design

The medicinal plant Maytenus ilicifolia is a commonly used phytomedicine for the treatment of gastritis. The high dose required and low density of these extracts make necessary a daily intake of several capsules, hindering adherence to the medication. The purpose of this work was to develop a suitable dosage form for the administration of Maytenus ilicifolia using effervescent granules. A 23 factorial design was used to study the physical characteristics of the granules (particle size distribution, repose angle, Carr index, scanning electron microscopy and disintegration time). Moisture stability was also determined. According to the experimental design, granule size is the most important factor in determining the flow characteristics of effervescent granules. In turn, the disintegration time is controlled by the content of sodium bicarbonate present in the effervescent mixture as well as the granule size. The stability of formulations when exposed to moisture is strongly influenced by the percentage of effervescent mixture present in the vegetal granules. Precautions in handling and storage should be taken to ensure the stability of these preparations. The effervescent granules produced from Maytenus ilicifolia met the pharmacopoeial quality parameters, with appropriate mechanical and physical characteristics and proved to be a promising vehicle for plant extracts.

Design and evaluation of gastroretentive levofloxacin floating mini-tablets-in-capsule system for eradication of Helicobacter pylori

Gastroretentive levofloxacin (LVF) floating mini-tablets for the eradication of Helicobacter pylori (H. pylori) were prepared using the matrix forming polymer hydroxypropyl methylcellulose (HPMC K100M), alone or with Carbopol 940P in different ratios by wet granulation technique. Buoyancy of mini-tablets was achieved by an addition of an effervescent mixture consisting of sodium bicarbonate and anhydrous citric acid to some formulations. The prepared mini-tablets were evaluated for weight variation, thickness, friability, hardness, drug content, in vitro buoyancy, water uptake and in vitro release. The optimized formula was subjected to further studies: FT-IR, DSC analysis and in vivo examination in healthy volunteers. The prepared mini-tablets exhibited satisfactory physicochemical characteristics. Incorporation of gas-generating agent improved the floating parameters. HPMC K100M mini-tablet formulation (F1) offered the best controlled drug release (>8h) along with floating lag time <1s and total floating time >24h. The obtained DSC thermograms and FT-IR charts indicated that there is no positive evidence for the interaction between LVF and ingredients of the optimized formula. The in vivo test confirmed the success of the optimized formula F1 in being retained in the stomach of the volunteers for more than 4h. LVF floating mini-tablets based on HPMC K100M is a promising formulation for eradication of H. pylori.

Studies on development and characterization of gastroretentive drug delivery system for antibiotics: Cefdinir

Aims/objectiveOral SR gastroretentive dosage forms offer many advantages for drugs having absorption from upper GIT and improve the bioavailability of medications that are characterized by narrow absorption window. Cefdinir is a third generation cephalosporin with broad spectrum of activity with low bioavailability (20–30%) and short biological half life (1–2 h). It has better absorption from upper part of gastrointestinal tract. The purpose of present study was to formulate and develop a new GRDDS using bilayered tablet technology for cefdinir as a model drug. MethodsCefdinir bilayer tablets (CBT) were prepared by using double compression cup and core method. First layer, floating matrix layer contained different rate retarding polymers and effervescent mixture. Second layer is loading layer contained cefdinir and fast releasing components (soluble starch, sodium bicarbonate and citric acid). All CBT were evaluated for their pre and post compression parameters. ResultsPrecompression and post compression parameter of all CBT were within the pharmacopeial limits. In vitro buoyancy behavior and matrix integrity study revealed that FLT of optimized formulation was 1.57 ± 0.52 min and the tablet remained floatable throughout the study. In vitro drug release of optimized CBT follows initially first order release upto 30 min (till their release of loading layer), then zero order release upto 12 h and kinetic profile followed the Peppas (R2 = 0.9838) and zero order (R2 = 0.9986). FTIR studies revealed no drug–excipients interactions. Stability studies conducted for optimized formulation did not show any change in physical appearance, drug content, floatability, matrix integrity. ConclusionKinetics of CBT showed biphasic release in the first phase, immediate dose was released in less than 60 min and second phase was released from matrix layer as a controlled zero order fashion. Cefdinir is a suitable drug for development of gastroretentive bilayer tablet.

Formulation and Characterization of Ciclopirox Olamine Mucoadhesive Effervescent Tablets for Vaginal Delivery

The study was aimed to design and evaluate a new effervescent mucoadhesive vaginal drug delivery system for ciclopirox olamine (CPO), a broad-spectrum antifungal, antibacterial, and anti-inflammatory agent for effective treatment in vaginal candidiosis. Various polymers like Polyox 303, Carbopol 974P, HPMC K4M, Sodium CMC, HPC, Sodium Alginate, Xanthan Gum, Polycarbophil and Chitosan were used in the formulation of CPO effervescent mucoadhesive vaginal tablet (EMVT) employing direct compression as a method of preparation. The effervescent mixture (citric acid and sodium bicarbonate) was incorporated into the formulations to aid quick wetting and mucoadhesion of tablet followed by drug release modulation. The amount of polymer blends and effervescent mixture was optimized using 32 full factorial design. The swelling, mucoadhesive strength and in-vitro release were studied as dependent responses. The ex-vivo mucoadhesion was determined by modified mucoadhesion assembly. The ex-vivo residence test was carried out by modified USP dissolution test apparatus. In vitro anti-fungal activity of the CPO EMVT was determined in comparison to Candid®-V3 tablet. A good sustained effect and a moderate mucoadhesion (0.31N to 0.67N) were obtained with tablets containing HPMC K4M: Polyox 303 (1:1.4) and effervescent mixture (1:3). Ex-vivo mucoadhesion time of all the formulations was in the range of 8 to 24 h. The effervescent CPO tablet showed significantly higher in-vitro antifungal activity as compare to Candid®-V3 tablet (p&lt; 0.05). The results of short term stability revealed stable characteristics of optimized formulation. The proposed formulation may provide a potential antifungal activity against Candida albicans.&#x0D;

Co-processing Plant Extracts for Improvement of Their Pharmacotechnic Properties

ABSTRACT: The herbal Espinheira Santa (Maytenus ilicifolia) can ingested in capsules for treatment of injuries from digestive tract, such as gastritis. However, the large amount of drug administered dose medication adherence difficult, so this study sought an alternative by formulating effervescent granules facilitating drug intake. The obtained granules made by wet and effervescent mixture of citric acid, sodium carbonate and sodium bicarbonate at different concentrations, totaling eight formulations, in addition to lactose as diluent and disintegrant in the composition. The granules were produced in sizes from 1 and 2mm. Rheological tests were compared against the dry extract, analyzed the average particle sizes of beads, mapped its surface by scanning electron microscopy and evaluated their behavior effervescent. The flow properties of the granules showed better values than the dry extract. The co-processed formulations showed average particle sizes distributed closed, where 1mm time effervescence had smaller, respecting all formulations, pharmacopeial limits of maximum 5 minutes. The preparation of effervescent granules Espinheira Santa proved to be a good alternativel, once that have easy preparation, low cost, excellent flow and rapid disintegration. Keywords: Espinheira Santa, effervescent granules, dry extract.

Programmed delivery of verapamil hydrochloride from tablet in a capsule device

The aim of the present work was to develop a programmed drug delivery system which would be able to release the drug after 6 h of lag time by use of hydrophilic polymers. The capsule body was made impermeable by use of formaldehyde vapor treatment, while the cap was untreated. The capsule was filled with two layered tablets (tablet-in-capsule), followed by a sodium bicarbonate:citric acid mixture (SBCM) and lactose as bulking agent. Sodium alginate, chitosan, HPMC K15 and chitosan:sodium alginate complex (CSAC) were used as the rate modulating layer. Through combined use of HPMC K15 and adjusting the ratio of CSAC, the desired lag time of 6 h was obtained. The effect of the bulking agents on the lag time were also studied and it was found that the lag time was decreased with higher amounts of lactose, and delayed dissolution and decreased lag time was observed at higher amount of effervescent mixture.

Poly-lactide-co-glycolide nanoparticles containing voriconazole for pulmonary delivery: in vitro and in vivo study

Poly-lactide-co-glycolide nanoparticles (207–605 nm) containing voriconazole (VNPs) were developed using a multiple-emulsification technique and were also made porous during preparation in presence of an effervescent mixture for improved pulmonary delivery. Pulmonary deposition of the particles was studied using a customized inhalation chamber. VNPs had a maximum of 30% (w/w) drug loading and a zeta potential (ZP) value around −20 mV. In the initial 2 hours, 20% of the drug was released from VNPs, followed by sustained release for 15 days. Porous particles had a lower mass median aerodynamic diameter (MMAD) than nonporous particles. Porous particles produced the highest initial drug deposition (~120 μg/g of tissue). The drug was detectable in lungs until 7 days and 5 days after administration, for porous and nonporous particles, respectively. VNPs with improved drug loading were successfully delivered to murine lungs. Porous nanoparticles with lower MMADs showed better pulmonary deposition and sustained presence in lungs. From the Clinical EditorIn this paper, voriconazole-containing porous nanoparticles were studied for inhalational delivery to lung infections in a murine model, demonstrating prolonged half-life and improved pulmonary deposition.

Development and evaluation of glipizide floating tablet

The purpose of this research was to develop a novel gastroretentive drug delivery system based on effervescent technology for controlled delivery of active agent. Glipizide, a poorly soluble drug has been used as a model drug and an attempt has been made to improve the solubility of drug by the incorporation of accelerating agents, such as dispersant, alkalizing agent in conjunction with hydrophilic swellable polymer such as hydroxypropylmethylcellulose and present it in the form of gastroretentive floating tablets, which are designed to provide the desired controlled and complete release of drug for a prolonged period of time. Floating tablets were prepared by direct compression method. Hydroxypropylmethylcellulose (HPMC K15M, HPMC K100M) and Carbopol 940P were incorporated for gelforming properties. Buoyancy was achieved by adding an effervescent mixture of sodium bicarbonate and anhydrous citric acid. The optimized formulation (F7) exhibited 98.60 % drug release in 24 h, while the buoyancy lag time was 140 s. In vitro drug release kinetics were found to follow both the zero order and the Korsmeyer and Peppas equation. The release of glipizide from the formulations was found to be non-Fickian type. Evaluation of gastric retention using X-ray imaging studies were performed on rabbit to justify the increased gastric residence time of the dosage form in the stomach, based on the floating principle. Optimized formulation (F7) showed no significant change in physical appearance, drug content, total buoyancy time, or in vitro dissolution pattern after storage at 40 °C/75 % relative humidity for 1 month.

Development and Evaluation of Gastroretentive Floating Tablets of Glipizide Based on Effervescent Technology

The purpose of this research was to develop a novel gastroretentive drug delivery system based on effervescent technology for controlled delivery of active agent. Glipizide, a poorly soluble drug has been used as a model drug and an attempt has been made to improve the solubility of drug by the incorporation of accelerating agents, such as dispersant, alkalising agent in conjunction with hydrophilic swellable polymer such as hydroxypropylmethylcellulose and present it in the form of gastroretentive floating tablets, which are designed to provide the desired controlled and complete release of drug for prolonged period of time. Floating tablets were prepared by direct compression method. Hydroxypropylmethylcellulose (HPMC K15M, HPMC K100M), Carbopol 940P, were incorporated for gelforming properties. Buoyancy was achieved by adding an effervescent mixture of sodium bicarbonate and anhydrous citric acid. The optimized formulation (F7) exhibited 98.60% drug release in 24 hrs, while the buoyancy lag time was 140sec. In-vitro drug release kinetics was found to follow both the Zero order and the Korsmeyer and Peppas equation (Table 7). The release of glipizide from the formulations was found to be non-fickian type. Evaluation of Gastric Retention Using X-Ray Imaging studies were performed on rabbit to justify the increased gastric residence time of the dosage form in the stomach, based on the floating principle. Optimized formulation (F7) showed no significant change in physical appearance, drug content, total buoyancy time, or in vitro dissolution pattern after storage at 40°C/75% (Figure 5) relative humidity for 1 month.

Effect of formulation parameters on the drug release and floating properties of gastric floating two-layer tablets with acetylsalicylic acid

Floating dosage forms of acetylsalicylic acid, used for its antithrombotic effect, were developed to prolong gastric residence time and increase bioavailability. In the two-layer tablet formulation, hydroxypropyl methylcellulose (HPMC) of high viscosity and an effervescent mixture of citric acid and sodium bicarbonate formed the floating layer. The release layer contained the drug, direct tableting agent and different types of matrix-forming polymers such as HPMC of low viscosity, sodium carboxymethylcellulose and chitosan. Tablets were prepared using a direct compression technique. The effect of formulation variables on physicochemical and floating properties and the drug release from tablets were investigated. Floating ability was dependent on the amount of effervescent agent and gel-forming polymer of the floating layer. Drug release was prolonged to 8 hours by changing the type and viscosity of the matrix-forming polymer in the drug-loading layer and all formulations showed a diffusion release mechanisms.

Development of effervescent tablets containing benznidazole complexed with cyclodextrin

Benznidazole (BNZ), the primary chemotherapy agent used to treat Chagas disease, has poor aqueous solubility, which results in low bioavailability. The purpose of this work was to develop stable effervescent tablets using an inclusion complex of BNZ with cyclodextrin (CD). In the first phase, different CDs were evaluated according to their ability to improve the aqueous solubility of BNZ. Then, inclusion complexes of BNZ in the solid state were produced by the kneading method and the complexes were evaluated using several physical-chemical assays. Finally, effervescent tablets were prepared according to a complete 3(2) factorial design. The effects of the concentration of CD and effervescent mixture on the dissolution rate and physical stability of tablets were evaluated. Hydroxypropyl-β-cyclodextrin produced the greatest improvement in the aqueous solubility of BNZ, almost 20-times greater than the water system. Solid systems produced with BNZ and CD showed physical-chemical interactions and increased the drug dissolution rate, suggesting the formation of a true solid inclusion complex. Moreover, the effervescent matrix of the tablets was effective in improving the dissolution behaviour of BNZ complexed with CD. Effervescent tablets produced using an inclusion complex of BNZ with CD suggest a possible improvement in the bioavailability of BNZ, and this could represent a relevant advance in Chagas therapy.

Development and In Vivo Floating Behavior of Verapamil HCl Intragastric Floating Tablets

A novel gastro retentive controlled release drug delivery system of verapamil HCl was formulated in an effort to increase the gastric retention time of the dosage form and to control drug release. Hydroxypropylmethylcellulose (HPMC), carbopol, and xanthan gum were incorporated for gel-forming properties. Buoyancy was achieved by adding an effervescent mixture of sodium bicarbonate and anhydrous citric acid. In vitro drug release studies were performed, and drug release kinetics was evaluated using the linear regression method. The optimized intragastric floating tablet composed of 3:2 of HPMC K4M to xanthan gum exhibited 95.39% drug release in 24 h in vitro, while the buoyancy lag time was 36.2 s, and the intragastric floating tablet remained buoyant for >24 h. Zero-order and non-Fickian release transport was confirmed as the drug release mechanism from the optimized formulation (F7). X-ray studies showed that total buoyancy time was able to delay the gastric emptying of verapamil HCl intragastric floating tablet in mongrel dogs for more than 4 h. Optimized intragastric floating tablet showed no significant change in physical appearance, drug content, total buoyancy time, or in vitro dissolution pattern after storage at 40 degrees C/75% relative humidity for 3 months.