scholarly journals Formulation and Development of Oral Fast-Dissolving Films Loaded with Nanosuspension to Augment Paroxetine Bioavailability: In Vitro Characterization, Ex Vivo Permeation, and Pharmacokinetic Evaluation in Healthy Human Volunteers

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1869
Author(s):  
Ahmed Hassen Elshafeey ◽  
Rania Moataz El-Dahmy
Keyword(s):  
Buccal Mucosa ◽  
Water Solubility ◽  
Ex Vivo ◽  
In Vitro Dissolution ◽  
Healthy Human ◽  
Disintegration Time ◽  
Casting Technique ◽  
Ex Vivo Permeation ◽  
Human Volunteers

Paroxetine (PX) is the most potent serotonin reuptake inhibitor utilized in depression and anxiety treatment. It has drawbacks, such as having a very bitter taste, low water solubility, and undergoing extensive first pass metabolism, leading to poor oral bioavailability (<50%). This work aimed to develop and optimize palatable oral fast-dissolving films (OFDFs) loaded with a paroxetine nanosuspension. A PX nanosuspension was prepared to increase the PX solubility and permeability via the buccal mucosa. The OFDFs could increase PX bioavailability due to their rapid dissolution in saliva, without needing water, and the rapid absorption of the loaded drug through the buccal mucosa, thus decreasing the PX metabolism in the liver. OFDFs also offer better convenience to patients with mental illness, as well as pediatric, elderly, and developmentally disabled patients. The PX nanosuspension was characterized by particle size, poly dispersity index, and zeta potential. Twelve OFDFs were formulated using a solvent casting technique. A 22 × 31 full factorial design was applied to choose the optimized OFDF, utilizing Design-Expert® software (Stat-Ease Inc., Minneapolis, MN, USA). The optimized OFDF (F1) had a 3.89 ± 0.19 Mpa tensile strength, 53.08 ± 1.28% elongation%, 8.12 ± 0.13 MPa Young’s modulus, 17.09 ± 1.30 s disintegration time, and 96.02 ± 3.46% PX dissolved after 10 min. This optimized OFDF was subjected to in vitro dissolution, ex vivo permeation, stability, and palatability studies. The permeation study, using chicken buccal pouch, revealed increased drug permeation from the optimized OFDF; with a more than three-fold increase in permeation over the pure drug. The relative bioavailability of the optimized OFDF in comparison with the market tablet was estimated clinically in healthy human volunteers and was found to be 178.43%. These findings confirmed the success of the OFDFs loaded with PX nanosuspension for increasing PX bioavailability.

scholarly journals Formulation development of methylprednisolone dispersible tablets using quality by design approach

2019 ◽  
Vol 9 (1-s) ◽  
pp. 229-239
Author(s):  
J Nandhini ◽  
AN Rajalakshmi
Keyword(s):  
Patient Compliance ◽  
Quality By Design ◽  
Water Solubility ◽  
Magnesium Stearate ◽  
In Vitro Dissolution ◽  
Direct Compression ◽  
Formulation Development ◽  
Disintegration Time ◽  
Dispersible Tablets

The objective of this study was to enhance the solubility of Methylprednisolone by choosing micronized form of drug and to enhance patient compliance by formulating it as dispersible tablets using quality by design (QbD) approach. Dispersible tablets of Methylprednisolone were developed by 23 factorial design. In this study independent variables were concentrations of MCC 102, CCS and Magnesium stearate and dependent variables were disintegration time, hardness and dissolution. The resulting data was fitted into Design Expert Software (Trial Version) and analyzed statistically using analysis of variance (ANOVA). The response surface plots were generated to determine the influence of concentration of MCC 102, CCS and magnesium stearate on responses. The tablets were prepared by direct compression method by choosing micronized form of drug and formulations were evaluated for the standard of dispersible tablets. Results showed that no significant drug-polymer interactions in FTIR studies. According to QbD suggestion the formulation O1 (Desirability- 0.73) with MCC-38mg, CCS-3.5mg and magnesium stearate-2.5mg was formulated and evaluated. The disintegration time was found to be 69 seconds, hardness was found to be 64N and in vitro dissolution with in 30minutes. Optimized O1 formulation was within the limits of standards of dispersible tablets with increased water solubility and better patient compliance. Stability study on optimized O1 formulation showed that there is no significant changes during study period. Thus, O1 formulation was found to be stable. The study indicates that formulation of Methylprednisolone dispersible tablets by using QbD approach is a promising formulation development method. Keywords: Dispersible tablets, Methylprednisolone, Direct compression, Quality by Design and ANOVA.

scholarly journals FORMULATION AND EVALUATION OF FAST DISSOLVING ORAL FILM OF ANTI-ALLERGIC DRUG

2018 ◽  
Vol 6 (3) ◽  
pp. 5-16 ◽  
Author(s):  
ABRAHAM LINKU ◽  
JOSEPH SIJIMOL
Keyword(s):  
Ex Vivo ◽  
Methyl Cellulose ◽  
Moisture Loss ◽  
In Vitro Dissolution ◽  
Content Uniformity ◽  
Onset Of Action ◽  
Disintegration Time ◽  
Permeation Study ◽  
Weight Variation

The aim of present work was the development of fast dissolving oral film of Loratadine to overcome the limitations of current routes of administration, to provide immediate action and increase the patient compliance. To improve the bioavailability of the drug, fast dissolving oral film were formulated using different grades of Hydroxy Propyl Methyl Cellulose(HPMC) and various plasticizers like Polyethylene Glycol(PEG) 400, glycerol, Propylene glycol(PG) by solvent casting method. The formulated films were evaluated for film thickness, surface pH, folding endurance, weight variation, % moisture loss, exvivo permeation study, tensile strength, % elongation, drug content uniformity, in vitro dissolution studies,in vitro disintegration test and in vivo study. The optimized formulation (F9) containing HPMC E5 and glycerol showed minimum disintegration time (10.5 s), highest in vitrodissolution (92.5%) and satisfactory stability. Ex vivo permeation study of optimized formulation showed a drug release of 80.6% within 10 min. The milk induced leucocytosis inrat proved that fast dissolving oral films of Loratadine produced a faster onset of action compared to the conventional tablets. These findings suggest that fast dissolving oral film of Loratadine could be potentially useful for treatment of allergy where quick onset of action is required.

scholarly journals ASSESSING THE RATIONALE OF FDC CONTAINING OFLOXACIN AND AZOLES: DISSOLUTION, PERMEATION AND ANTIMICROBIAL STUDIES

2019 ◽  
pp. 36-42
Author(s):  
ATMARAM PAWAR ◽  
AKSHAY KAMBLE ◽  
SWATI KORAKE ◽  
VIVIDHA DHAPTE-PAWAR
Keyword(s):  
Ex Vivo ◽  
Synergistic Effects ◽  
Evaluation Study ◽  
In Vitro Dissolution ◽  
Diffusion Method ◽  
Fixed Dose ◽  
Shigella Boydii ◽  
Ex Vivo Permeation ◽  
The Individual

Objective: To study fixed-dose combinations (FDC) of antibacterial and antiprotozoal products (ofloxacin and azoles), prescribed for the treatment of diarrhea. Methods: Rationality of these FDC products was verified by assessing parameters such as drug content and release by assay and dissolution tests, respectively mentioned in the Indian Pharmacopoeia (IP). Amount of drug solubilized and permeated as per the Biopharmaceutics Classification System (BCS) was determined. Ex vivo permeation study was performed on the gut of goat using the everted gut sac technique. Antimicrobial efficacy in terms of minimum inhibitory concentration (MIC) was assessed using agar well diffusion method against Shigella boydii, the causative agent for diarrhea. Comparative studies were performed on an individual as well as combination doses of antibacterial and antiprotozoal products for the synergistic effects to assess the rationale of these FDC. Results: The BCS solubility of ciprofloxacin (CPX), norfloxacin (NFX) and tinidazole (TNZ) was high in acidic medium (pH 1-5) and decreased at pH above 5. The assay studies showed that the individual drug contents of FDC were within the IP limits. In vitro dissolution results for both, individual drugs and their combination illustrated 99 % drug release within 30 min in 0.01N HCl. Ex vivo permeation of TNZ was higher than CPX and NFX in individual drugs. No significant change in the permeation rate was observed for individual drugs and their FDC. CPX and NFX exhibited more antimicrobial activity in terms of inhibitory zones than their FDC with antiprotozoal TNZ, above 2.5 µg/ml MIC. The pharmaceutical, biopharmaceutical and antimicrobial evaluation study showed the similarity of FDC with the individual drugs. Conclusion: The study showed no significant data to justify the therapeutic advantage of FDC over individual drugs.

scholarly journals The safety profile of Bald’s eyesalve for the treatment of bacterial infections

2020 ◽  
Author(s):  
Blessing O Anonye ◽  
Valentine Nweke ◽  
Jessica Furner-Pardoe ◽  
Rebecca Gabrilska ◽  
Afshan Rafiq ◽  
...  
Keyword(s):  
Topical Application ◽  
Safety Profile ◽  
Bacterial Infections ◽  
Ex Vivo ◽  
Corneal Opacity ◽  
Healthy Human ◽  
Patch Tests ◽  
Human Volunteers

AbstractThe rise in antimicrobial resistance has prompted the development of alternatives, such as plant-derived compounds, to combat bacterial infections. Bald’s eyesalve, a remedy used in the Early Medieval period, has previously been shown to have efficacy against Staphylococcus aureus grown in an in vitro model of soft tissue infection. This remedy also had bactericidal activity against methicillin-resistant S. aureus (MRSA) in a chronic mouse wound. However, the safety profile of Bald’s eyesalve has not yet been demonstrated, and this is vital before testing in humans. Here, we determined the safety potential of Bald’s eyesalve using in vitro, ex vivo, and in vivo models representative of skin or eye infections. We also confirmed that Bald’s eyesalve is active against an important eye pathogen, Neisseria gonorrhoeae. Low levels of cytotoxicity were observed in eyesalve-treated cell lines representative of skin and immune cells. Results from a bovine corneal opacity and permeability test demonstrated slight irritation to the cornea that resolved within 10 minutes. The slug mucosal irritation assay revealed that a low level of mucus was secreted by slugs exposed to eyesalve, indicating mild mucosal irritation. We obtained promising results from mouse wound closure experiments; no visible signs of irritation or inflammation were observed. Our results suggest that Bald’s eyesalve could be tested further on human volunteers to assess safety for topical application against bacterial infections.ImportanceAlternative treatment for bacterial infections are needed to combat the ever increasing repertoire of bacteria resistant to antibiotics. A medieval plant-based remedy, Bald’s eyesalve, shows promise as a substitute for the treatment of these infections. For any substance to be effective in the treatment of bacterial infections in humans, it is important to consider the safety profile. This is a key consideration in order to have the necessary regulatory approval. We demonstrate the safety profile of Bald’s eyesalve using a variety of models, including whole-organ and whole-animal models. Our results show that Bald’s eyesalve is mildly toxic to cultured human cells, but potentially suitable for patch tests on healthy human volunteers to assess safety for later clinical trials. Our work has the potential to transform the management of diseases caused by bacterial infections, such as diabetic foot ulcers, through topical application of a natural product cocktail based on Bald’s eyesalve.

scholarly journals Cyclodextrin–Amphiphilic Copolymer Supramolecular Assemblies for the Ocular Delivery of Natamycin

Nanomaterials ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 745 ◽  
Author(s):  
Blanca Lorenzo-Veiga ◽  
Hakon Hrafn Sigurdsson ◽  
Thorsteinn Loftsson ◽  
Carmen Alvarez-Lorenzo
Keyword(s):  
Mixed Micelles ◽  
Water Solubility ◽  
Ex Vivo ◽  
Chorioallantoic Membrane ◽  
Ex Vivo Permeation ◽  
Hen’S Egg ◽  
Permeation Studies ◽  
20 Nm ◽  
In Situ Gelling

Natamycin is the only drug approved for fungal keratitis treatment, but its low water solubility and low ocular penetration limit its efficacy. The purpose of this study was to overcome these limitations by encapsulating the drug in single or mixed micelles and poly(pseudo)rotaxanes. Soluplus and Pluronic P103 dispersions were prepared in 0.9% NaCl and pH 6.4 buffer, with or without α-cyclodextrin (αCD; 10% w/v), and characterized through particle size, zeta potential, solubilization efficiency, rheological properties, ocular tolerance, in vitro drug diffusion, and ex vivo permeation studies. Soluplus micelles (90–103 nm) and mixed micelles (150–110 nm) were larger than Pluronic P103 ones (16–20 nm), but all showed zeta potentials close to zero. Soluplus, Pluronic P103, and their mixed micelles increased natamycin solubility up to 6.00-fold, 3.27-fold, and 2.77-fold, respectively. Soluplus dispersions and poly(pseudo)rotaxanes exhibited in situ gelling capability, and they transformed into weak gels above 30 °C. All the formulations were non-irritant according to Hen’s Egg Test on the Chorioallantoic Membrane (HET-CAM) assay. Poly(pseudo)rotaxanes facilitated drug accumulation into the cornea and sclera, but led to lower natamycin permeability through the sclera than the corresponding micelles. Poly(pseudo)rotaxanes made from mixed micelles showed intermediate natamycin diffusion coefficients and permeability values between those of Pluronic P103-based and Soluplus-based poly(pseudo)rotaxanes. Therefore, the preparation of mixed micelles may be a useful tool to regulate drug release and enhance ocular permeability.

Development and characterization of sublingual films for enhanced bioavailability of selegiline hydrochloride

2021 ◽  
Vol 12 (2) ◽  
pp. 159-174
Author(s):  
Sara Salatin ◽  
Raziyeh Asadi ◽  
Mitra Jelvehgari
Keyword(s):  
Ex Vivo ◽  
Alternative Pathway ◽  
Physicochemical Characteristics ◽  
Polymer Composition ◽  
Disintegration Time ◽  
In Vitro Drug Release ◽  
Ex Vivo Permeation ◽  
Permeation Studies

Low oral bioavailability of selegiline hydrochloride (SH) is primarily due to extensive first-pass metabolism and hence the need for an alternative pathway of administration. Herein, we report the development of sublingual SH films. The films were formulated with varying polymer composition (F1-F6) and evaluated for physicochemical characteristics, in vitro drug release and ex vivo permeation studies. The film F2 demonstrated satisfactory weight (10.60 mg), folding endurance (>200), drug content (11.44 mg/cm2), disintegration time (68 s), mucoadhesive strength (47.7 N/cm2), and controlled release for 30 min. The permeation studies exhibited a higher ex vivo sublingual flux than that of the plain drug. This study concludes that the SH film can provide a potential opportunity for sublingual drug delivery.

scholarly journals FORMULATION AND EVALUATION OF FAST DISSOLVING SUBLINGUAL FILM OF PAROXETINE HYDROCHLORIDE FOR TREATMENT OF DEPRESSION

2019 ◽  
pp. 126-132
Author(s):  
RITA N WADETWAR ◽  
FARHEEN ALI ◽  
PRANITA KANOJIYA
Keyword(s):  
Ex Vivo ◽  
Drug Loading ◽  
Physical Property ◽  
Systemic Absorption ◽  
Systemic Delivery ◽  
Onset Of Action ◽  
Disintegration Time ◽  
Casting Technique ◽  
Paroxetine Hydrochloride

Objective: Oromucosal route could be an alternative over the conventional route for paroxetine hydrochloride (PXH) as it offers direct systemic delivery, by avoiding extensive first-pass metabolism, which results in poor systemic absorption. The film dissolves quickly when placed in mouth without need of water thus helpful in providing rapid onset of action. Methods: Fast dissolving film of PXH was prepared using Pullulan in various combinations of 32 full factorial design by solvent casting technique. Prepared films were subjected to mechanical, in vitro, and ex vivo characterization. Results: The physicochemical characteristics such as mass uniformity, thickness, surface pH, and folding endurance were found satisfactory. The formulation (F3) containing 4% w/v Pullulan showed maximum release 94.31% and ex vivo permeation 92.67% through goat oral mucosa in 15 min. Uniform drug loading was observed in all the batches with disintegration time <25 s. Fourier transform infrared spectroscopy study revealed the compatibility of drug with polymer. Scanning electron microscopy revealed that there was uniform mixing of all ingredients. Optimized batch F3 was found to be stable for 1 month as no significant changes were observed in % cumulative drug release and weight of film. Conclusion: Pullulan a natural biodegradable polymer allocates good physical property to film. Hydrophilic nature of polymer imparts fast disintegrating property to film.

A Study of Mucoadhesive Bond Strength of Buccoadhesive Compacts for Systemic Drug Delivery: In-vitro/ In-vivo correlation

2001 ◽  
Vol 69 (2) ◽  
pp. 123-141
Author(s):  
D. Kumar ◽  
J. Balasubramaniam ◽  
J. Pandit
Keyword(s):  
Drug Delivery ◽  
Bond Strength ◽  
Buccal Mucosa ◽  
Healthy Human ◽  
Human Volunteers ◽  
Intestine Mucosa ◽  
Systemic Drug Delivery ◽  
Systemic Drug

Compacts prepared from binary combinations of Carbopol® 934 P (CP), Polycarbophil (Noveon® AA1, PC) and Hydroxy propyl cellulose (Klucel®, HPC) and coated on all but one flat surface with Poly Methyl Methacrylate - PMMA (chloroformic solution) were evaluated for mucoadhesive bond strength on a modified mucoadhesive bond strength apparatus using rabbit stomach mucosa (SM) and small intestine mucosa (SIM). In -vitro mucoadhesion tests indicated that the detachment force increased linearly with concentration of CP/PC in the compacts. Mucoadhesion of the compacts with SIM were higher when compared to SM. The compacts with higher proportions of CPIPC showed longer buccoadhesion time (time the compact remained in contact with the buccal mucosa) than HPC alone in humans. In-vivo buccoadhesevity of the coated compacts was studied in healthy human volunteers. An index was used to study the redness and ulceration of the contact buccal mucosa. Compacts with higher proportions of CP/PC showed longer buccoadhesion time than HPC alone. Significant correlation coefficient (r) values (P<0.01) were obtained between in-vitro fracture strength of the compacts and in-vivo buccoadhesion time. Hence, the in-vitro mucoadhesive model developed by us provides useful information on the residence time of the compact for systemic drug delivery in the oral cavity, and compacts containing less than 50% of CP/PC were safer to use in humans.

Formulation and Evaluation of Fast Disintigrating Meloxicam Tablets and Its Comparison with Marketed Product

2010 ◽  
Vol 2 (2) ◽  
Author(s):  
Suresh Kulkarni ◽  
Ranjit P. ◽  
Nikunj Patel ◽  
Someshwara B. ◽  
Ramesh B. ◽  
...  
Keyword(s):  
Water Absorption ◽  
In Vitro Dissolution ◽  
Thickness Variation ◽  
Wet Granulation ◽  
Disintegration Time ◽  
Absorption Ratio ◽  
Wetting Time ◽  
Fast Disintegrating Tablets ◽  
Cox 1

The present investigation deals with the formulation of fast disintegrating tablets of Meloxicam that disintegrate in the oral cavity upon contact with saliva and there by improve therapeutic efficacy. Meloxicam is a newer selective COX-1 inhibitor. The tablets were prepared by wet granulation procedure. The influence of superdisintegrants, crosspovidone, croscaremellose sodium on disintegration time, wetting time and water absorption ratio were studied. Tablets were evaluated for weight and thickness variation, disintegration time, drug content, in vitro dissolution, wetting time and water absorption ratio. The in vitro disintegration time of the best fast disintegrating tablets was found to be 18 sec. Tablets containing crospovidone exhibit quick disintegration time than tablets containing croscaremellose sodium. The fast disintegrating tablets of Meloxicam with shorter disintegration time, acceptable taste and sufficient hardness could be prepared using crospovidone and other excipients at optimum concentration.

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