scholarly journals Application of Nanopharmaceutics for Flibanserin Brain Delivery Augmentation Via the Nasal Route

Nanomaterials ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1270
Author(s):  
Osama A. A. Ahmed ◽  
Usama A. Fahmy ◽  
Shaimaa M. Badr-Eldin ◽  
Hibah M. Aldawsari ◽  
Zuhier A. Awan ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Methyl Cellulose ◽  
Molar Ratio ◽  
Peroral Administration ◽  
Brain Delivery ◽  
Box Behnken Design ◽  
Ex Vivo Permeation ◽  
Hydrophilic Lipophilic Balance ◽  
First Pass ◽  
Edge Activator

Flibanserin (FLB) is a nonhormonal medicine approved by the Food and Drug Administration (FDA) to treat the hypoactive sexual appetite disorder in females. However, the peroral administration of the medicine is greatly affected by its poor bioavailability as a result of its extensive first-pass effect and poor solubility. Aiming at circumventing these drawbacks, this work involves the formulation of optimized FLB transfersome (TRF) loaded intranasal hydrogel. Box–Behnken design was utilized for the improvement of FLB TRFs with decreased size. The FLB-to-phospholipid molar ratio, the edge activator hydrophilic lipophilic balance, and the pH of the hydration medium all exhibited significant effects on the TRF size. The optimized/developed TRFs were unilamellar in shape. Hydroxypropyl methyl cellulose based hydrogel filled with the optimized FLB TRFs exhibited an improved ex vivo permeation when compared with the control FLB-loaded hydrogel. In addition, the optimized TRF-loaded hydrogel exhibited higher bioavailability and enhanced brain delivery relative to the control hydrogel following intranasal administration in Wistar rats. The results foreshadow the possible potential application of the proposed intranasal optimized FLB-TRF-loaded hydrogel to increase the bioavailability and nose-to-brain delivery of the drug.

scholarly journals FORMULATION OF RIZATRIPTAN BENZOATE SUBLINGUAL TABLETS PREPARED BY DIRECT COMPRESSION WITH DIFFERENT BIOADHESIVE POLYMER: IN VITRO AND EX VIVO EVALUATION

2017 ◽  
Vol 10 (16) ◽  
pp. 36
Author(s):  
Harmanpreet Singh ◽  
Pooja Jaiswal ◽  
Suksham Gupta ◽  
Simerjit Singh
Keyword(s):  
Ex Vivo ◽  
Methyl Cellulose ◽  
Systemic Circulation ◽  
Direct Compression ◽  
Compression Process ◽  
Rizatriptan Benzoate ◽  
Dissolution Tests ◽  
Ex Vivo Permeation ◽  
Bioadhesive Polymers

  Objective: The current investigation deals with formulation and evaluation of fast disintegrating sublingual tablets of rizatriptan benzoate (RTB) to produce its intended therapeutic effect for acute treatment of migraine. When the drug is given by sublingual route, it overcomes the first pass metabolism and quick entry of drug in systemic circulation is obtained. It would result in fast pharmacological response hence faster relief from migraine which is an important criterion in migraine therapy.Methods: In this study, RTB sublingual tablets were prepared using direct compression process using various bioadhesive polymers such as sodium carboxymethyl cellulose, hydroxyl propyl methyl cellulose-K4M, and chitosan at various concentration ranging 0.5-5% w/w along with sodium starch glycolate (SSG) or cross carmellose sodium (CCS) as super disintegrants at different concentration ranging 2-8% w/w.Results: The tablets disintegrated quickly and dissolution tests conclude that RTB was released from the formulation within the compendial limits. The formulations batches (A8 and B8) containing 2% w/w chitosan along with 2% w/w SSG or CCS which disintegrate rapidly and show high dissolution and ex vivo permeation were selected as optimized formulations.Conclusion: The results obtained from the study showed that the bioavailability problem of the drug has been solved as the drug is given by sublingual route and it directly enters into systemic circulation. Furthermore, the formulation overcomes the problems associated with migraine attack as fast disintegrating technology is used.

scholarly journals FORMULATION, IN VITRO AND EX VIVO CHARACTERIZATION OF MUCOADHESIVE BUCCAL TABLETS FOR ANTIHYPERTENSIVE DRUG

2018 ◽  
Vol 11 (8) ◽  
pp. 402 ◽  
Author(s):  
Himabindu Peddapalli ◽  
Vasudha Bakshi ◽  
Narender Boggula
Keyword(s):  
Drug Release ◽  
Ex Vivo ◽  
Surface Ph ◽  
Ex Vivo Permeation ◽  
First Pass Metabolism ◽  
First Pass ◽  
Permeation Studies ◽  
Buccal Tablets ◽  
Pass Metabolism

Objective: Olmesartan belongs to a class of angiotensin II receptor blockers. It is used in the treatment of hypertension. However, it undergoes extensive hepatic first-pass metabolism, resulting in low oral bioavailability is about 26%. The aim of this study was to prepare and evaluate the mucoadhesive buccal tablets of olmesartan with a goal to increase the bioavailability and improve the patient compliance.Methods: Mucoadhesive buccal tablets were prepared by a direct compression technique using mucoadhesive polymers such as hydroxypropyl methylcellulose (HPMC K4M), sodium carboxymethylcellulose (SCMC), and Carbopol 934P. The tablets were evaluated for weight variation, thickness, hardness, friability, surface pH, swelling index, drug content uniformity, in vitro drug release, ex vivo mucoadhesive strength, ex vivo mucoadhesive time, and ex vivo permeation studies. The release kinetics was calculated to determine the drug release mechanism. Results: The physicochemical properties of all the formulations were shown to be within the limits. The optimized buccal tablets F2, F7, and F11 showed satisfactory drug release rates with the diffusion controlled mechanism. Optimized buccal tablets developed for olmesartan possess reasonable mucoadhesive strength, mucoadhesive time, and surface pH was in an acceptable salivary pH 6.76±0.28–6.89±0.34. The ex vivo permeation studies for optimized tablets were shown satisfactory drug permeation and could meet the target flux 0.991 mg h−1cm−2.Conclusion: The obtained results could be used as a platform to develop the buccal delivery of this drug, which bypasses the first-pass metabolism and results in the improvement of bioavailability. Hence, the present study concludes that the olmesartan could be delivered through the buccal route.

Formulation and Evaluation of Neuroactive Drug Loaded Chitosan Nanoparticle for Nose to Brain Delivery: In-vitro Characterization and In-vivo Behavior Study

2018 ◽  
Vol 16 (2) ◽  
pp. 123-135 ◽  
Author(s):  
Mohsin Qureshi ◽  
Mohd. Aqil ◽  
Syed Sarim Imam ◽  
Abdul Ahad ◽  
Yasmin Sultana
Keyword(s):  
Drug Release ◽  
Ex Vivo ◽  
Drug Loading ◽  
Brain Delivery ◽  
Permeation Study ◽  
Behavior Study ◽  
Ex Vivo Permeation ◽  
Chitosan Nanoparticle ◽  
Ex Vivo Permeation Study

Background: The present work was designed to explore the efficacy of neuroactive drug (risperidone) loaded chitosan lipid nanoparticle (RIS-CH-LNPs) to enhance the bioactivity in schizophrenia via the nasal route. </P><P> Methods: The three-factor and three-level formulation by design approach was used for optimization and their effects were observed on (Y1) size in nm, (Y2) % drug loading, and (Y3) % drug release. The optimized formulation RIS-CH-LNPopt was further evaluated for its surface morphology, ex-vivo permeation study, in-vivo behavior study, and stability study. The developed RIS-CH-LNPs showed nanometric size range with high drug loading and prolonged drug release. Results: The optimized formulation (RIS-CH-LNPopt) has shown the particle size (132.7 nm), drug loading (7.6 %), drug release (80.7 %) and further ex-vivo permeation study showed 2.32 fold enhancement over RIS-SUS(suspension). In-vivo behavior studies showed that RIS-CH-LNPopt is able to show significant greater bioefficacy as compared to RIS-SUS [intranasal (i.n), intravenous (i.v)]. The pharmacokinetic and brain/plasma ratio of developed chitosan nanoparticle was higher at all time-points as compared to RIS-SUS either given by intranasal or intravenous route that proves the direct nose to brain transport pathway of the drug via nasal administration. The developed chitosan nanoparticle increases nose to brain drug delivery as compared to the dispersion of equivalent dose. The findings of this study substantiate the existence of a direct nose-to-brain delivery route for RIS-CH-LNPs.

scholarly journals Gamma oryzanol niosomal gel for skin cancer: formulation and optimization using quality by design (QbD) approach

AAPS Open ◽  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Harsh S. Shah ◽  
Ankit Gotecha ◽  
Dolly Jetha ◽  
Amarjitsing Rajput ◽  
Aditi Bariya ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Quality By Design ◽  
Rice Bran Oil ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Molar Ratio ◽  
Ex Vivo Permeation ◽  
Permeation Studies ◽  
Niosomal Gel ◽  
Gamma Oryzanol

AbstractSkin cancer is fifth most diagnosed disease in human population due to ultraviolet radiation (UV) exposure. Gamma oryzanol (OZ) is a natural antioxidant, and it also has skin anti-aging properties. OZ is naturally found in rice bran oil. The main aim of the present work was to optimize OZ niosomal formulation using quality by design approach including one variable at a time and full factorial design. Niosomes were prepared by solvent injection method and characterized for size, polydispersity index, drug entrapment, and transmission electron microscopy. The optimized batch obtained at X1 [drug to span 60 molar ratio (1:5)], X2 [volume of hydration (75 mL)], and X3 [stirring speed (2500 rpm)] to Y1 [average vesicle size (196.6 nm)] and Y2 [entrapment efficiency (78.31%)] as dependent variables. The optimized OZ noisomes were formulated by niosomal gel to provide improved physicochemical stability upon topical application against UV. The niosomal gel was characterized using pH meter, viscometer, Draize test for skin irritancy, ex vivo permeation studies, and stability studies. Ex vivo permeation studies of OZ niosomal gel not only showed fourfold higher permeation but also exhibited better drug retention in dermal layers of skin as compared to OZ gel. Quality Target Product Profile of OZ niosomal formulation was generated. Risk analysis of optimized OZ gel suggested most critical quality attributes (CQAs) and critical process parameters (CPPs) to be characterized as low risk. Thus, γ-oryzanol niosomal gel for topical use can serve as a promising prophylactic treatment in skin cancer, and the developed prototype formulation can be further extended to future newly discovered drugs with similar characteristics. Graphical abstract

scholarly journals Constant Voltage Iontophoresis Technique to Deliver Terbinafine via Transungual Delivery System: Formulation Optimization Using Box–Behnken Design and In Vitro Evaluation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1692
Author(s):  
Anroop B. Nair ◽  
Bandar E. Al-Dhubiab ◽  
Jigar Shah ◽  
Bapi Gorain ◽  
Shery Jacob ◽  
...  
Keyword(s):  
Low Voltage ◽  
Ex Vivo ◽  
Topical Therapy ◽  
Nail Plate ◽  
Drug Accumulation ◽  
Constant Voltage ◽  
Box Behnken Design ◽  
Ex Vivo Permeation ◽  
Transungual Delivery

Topical therapy of antifungals is primarily restricted due to the low innate transport of drugs through the thick multi-layered keratinized nail plate. The objective of this investigation was to develop a gel formulation, and to optimize and evaluate the transungual delivery of terbinafine using the constant voltage iontophoresis technique. Statistical analysis was performed using Box–Behnken design to optimize the transungual delivery of terbinafine by examining crucial variables namely concentration of polyethylene glycol, voltage, and duration of application (2–6 h). Optimization data in batches (F1–F17) demonstrated that chemical enhancer, applied voltage, and application time have influenced terbinafine nail delivery. Higher ex vivo permeation and drug accumulation into the nail tissue were noticed in the optimized batch (F8) when compared with other batches (F1–F17). A greater amount of terbinafine was released across the nails when the drug was accumulated by iontophoresis than the passive counterpart. A remarkably higher zone of inhibition was observed in nails with greater drug accumulation due to iontophoresis, as compared to the passive process. The results here demonstrate that the optimized formulation with low voltage iontophoresis could be a viable and alternative tool in the transungual delivery of terbinafine, which in turn could improve the success rate of topical nail therapy in onychomycosis.

scholarly journals FORMULATION AND EVALUATION OF IVABRADINE HYDROCHLORIDE LOADED TRANSFERSOMAL GEL FOR TRANSDERMAL DELIVERY

2020 ◽  
pp. 295-301
Author(s):  
GITA CHAURASIA ◽  
NARENDRA LARIYA
Keyword(s):  
Drug Release ◽  
Ex Vivo ◽  
Chronic Stable Angina ◽  
Phosphate Buffer Solution ◽  
Gelling Agent ◽  
Stability Studies ◽  
In Vitro Drug Release ◽  
Ex Vivo Permeation ◽  
Hydrophilic Lipophilic Balance

Objective: Aim of this study was to develop the topical delivery containing ivabradine hydrochloride (IVH) loaded transpersonal gel for symptomatic treatment of chronic stable angina pectoris in coronary artery disease. Methods: Different hydrophilic-lipophilic balance (HLB) values of surfactants-tween-80, span-80 and sodium deoxycholate (SDC) were investigated to prepare transfersomes (TFs)respectively, with different concentration of soya phosphatidylcholine and 10% v/v ethanol in phosphate buffer solution (pH 6.8) by conventional rotary evaporation sonication method. The prepared formulations were evaluated for percentage entrapment efficiency (%EE), deformability index (DI), turbidity, vesicle shape and size, in vitro drug release study and stability. SEM was done on selected formulation F8 and liposome formulation (LF). Gel was prepared by using carbopol-940 as a gelling agent with propylene glycol, polyethylene glycol solution as permeation enhancer by 32 factorial design optimization methods. The developed gel was evaluated for pH, viscosity, drug content, ex-vivo permeation studies and stability studies of TFs-gel. This was compared with LF-gel prepared by same procedure. Results: Maximum % EE (78.4±0.94), suitable vesicular size (128.6 nm) and maximum DI (34.9±1.9) was found in TFs-TW-80 and selected for gel development. In vitro drug release data from TFs-TW-80, plain drug solution and liposomal formulation (LF) revealed that % cumulative drug released in TFs-TW-80 was found maximum (89.5±0.12 %) in 20 min than others. It was 2.1 times higher than LF and 3.3 times higher than the plain drug. SEM study showed spherical shape of vesicles. The drug contents in the TFs and LF gels were found to be 92 to 95%w/w. Partition coefficient for TFs-loaded gel was 1.04±0.03. Ex vivo permeation study from hairless rat skin showed that permeation of drug is described by firstly first-order kinetics than zero-order kinetics. The drug released from TFs-gel was found to be 1.7 times higher than LF-gel and about 1.9 times higher than plain drug. Flux from TFs-gel was 2.04 times greater than LF-gel and 3.28 times more than plan drug. Stability studies indicated that suitable storage condition for developed gel was temperature 25 °C or less, where the pH, potency and therapeutic efficacy of formulations remain constant. Conclusion: Thus, transdermal route has become one of the most successful and innovative focus for research in drug delivery of IVH loaded TFs-TW-80 to increase stability and bioavailability.

scholarly journals Muco-adhesive buccal tablets of candesartan cilexetil for oral delivery: preparation, in-vitro and ex-vivo evaluation

2021 ◽  
Vol 11 (1-s) ◽  
pp. 35-42
Author(s):  
Kumara Swamy Samanthula ◽  
Agaiah Goud Bairi ◽  
CB Mahendra Kumar
Keyword(s):  
Candesartan Cilexetil ◽  
Ex Vivo ◽  
Methyl Cellulose ◽  
Carboxy Methyl Cellulose ◽  
First Pass Metabolism ◽  
First Pass ◽  
Buccal Tablets ◽  
Pass Metabolism ◽  
Carboxy Methyl

Candesartan cilexetil (CC) is an angiotensin II-receptor blocker (ARB). The antihypertensive effect of CC 4-16 mg/day was as great as that of other once-daily dosage regimens. Candesartan cilexetil has high first-pass metabolism and low oral bioavailability. The bioavailability of such drugs may be significantly improved if delivered through the buccal route; hence mucosal delivery is one of the alternative methods of systemic drug delivery. This study’s objective was to develop mucoadhesive buccal tablets of candesartan cilexetil using carbopol-934P, hydroxyl propyl methyl cellulose (HPMC), Eudragit RLPO, and sodium carboxy methyl cellulose (Na-CMC) as mucoadhesive polymers. Prepared CC buccal tablet formulations were evaluated for an optimized system based on physicochemical properties, ex-vivo residence time, in-vitro, and ex vivo permeation studies. The evaluation parameters of the tablets were within the acceptable Pharmacopoeial limits. However, the swelling and bio-adhesive time were increased with increasing polymer concentrations. The in-vitro release research shown that buccal tablets with sodium carboxy methyl cellulose (Na-CMC) exhibited a higher release than all other formulations and have been considered as optimized CC formulation. The release mechanism from kinetic methods suggests that the drug release follows zero-order kinetics with a diffusion mechanism. Further, in-vivo research in animal fashions is required to prove the bioavailability performance of the formulation. Keywords: Candesartan cilexetil, mucoadhesive buccal tablets, first-pass metabolism, bioavailability.

scholarly journals PRONIOSOMAL GEL MEDIATED TRANSDERMAL DELIVERY OF GLIBENCLAMIDE AND ATENOLOL COMBINATION: EXVIVO AND PHARMACODYNAMIC STUDIES

2021 ◽  
pp. 242-248
Author(s):  
P. ANITHA ◽  
S. V. SATYANARAYANA
Keyword(s):  
Transdermal Delivery ◽  
Ex Vivo ◽  
Skin Irritation ◽  
Prediction Method ◽  
Albino Rats ◽  
Box Behnken Design ◽  
Steady State Flux ◽  
Ex Vivo Permeation ◽  
Diabetic Hypertensive Patient ◽  
Wistar Albino Rats

Objective: The objective of the present work was to develop an optimized dosage form for treating comorbidity in combination and evaluate it for its pharmacodynamic performance in male Wistar albino rats. Methods: Transdermal proniosomal gel for Combination of Glibenclamide (GLB) and Atenolol (ATN) was developed and optimized by Box Behnken design. This optimized combinational proniosomal gel (OCPG), which was selected by a point prediction method, was evaluated for its ex vivo, skin irritation studies and pharmacodynamic activities of both drugs in rats in comparison with its oral therapy. Results: The ex-vivo permeation behavior through different skins was studied and the findings were also confirmed by the values of the steady-state flux (Jss). The OCPG observed an increase of more than twice in the cumulative amount of impregnated drugs compared to pure drug films. The study on skin irritation revealed the non-irritability of the developed OCPG applied. OCPG significantly showed sustained hypoglycemic activity in rats (p<0.001), when compared to orally treat animals up to 24 h. Systolic blood pressure (SBP) lowering effect of OCPG was found to be significant (p<0.02), when compared to orally treat rats up to 24 h. However, the reduction was slow and sustained in the case of OPCG where a significant response was observed in the performed studies. Conclusion: Overall, the results show that controlled release GLB and ATN proniosomes offer a useful and promising transdermal delivery system. Henceforth this may be an achievement in treating the diabetic hypertensive patient.

Cross-linked methyl cellulose/graphene oxide rate controlling membranes for in vitro and ex vivo permeation studies of diltiazem hydrochloride

RSC Advances ◽  
2016 ◽  
Vol 6 (42) ◽  
pp. 36136-36145 ◽  
Author(s):  
Gunjan Sarkar ◽  
Nayan Ranjan Saha ◽  
Indranil Roy ◽  
Amartya Bhattacharyya ◽  
Arpita Adhikari ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Ex Vivo ◽  
Methyl Cellulose ◽  
Diltiazem Hydrochloride ◽  
Permeability Characteristics ◽  
Ex Vivo Permeation ◽  
Permeation Studies ◽  
Hypertensive Drug

Permeability characteristics of the anti-hypertensive drug, diltiazem hydrochloride, from uncross-linked and cross-linked methylcellulose (MC)/graphene oxide (GO) rate controlling membranes (RCMs) were investigated.

Development and Ex-vivo Evaluation of Topiramate Mucoadhesive Nanoparticles for Intranasal Delivery

2020 ◽  
Vol 13 (6) ◽  
pp. 5250-5255
Author(s):  
Ashwin Kumar Tulasi ◽  
Anil Goud Kandhula ◽  
Ravi Krishna Velupula
Keyword(s):  
Particle Size ◽  
Nasal Mucosa ◽  
Intranasal Administration ◽  
Ex Vivo ◽  
Chemical Properties ◽  
Brain Targeting ◽  
Oral Tablet ◽  
Promising Alternative ◽  
Ex Vivo Permeation

Topiramate is a second-generation antiepileptic drug used in partial, generalized seizures as an oral tablet. Oral route of administration is most convenient but shows delayed absorption. Moreover, in emergency cases, parenteral administration is not possible as it requires medical assistance. Hence, the present study was aimed to develop topiramate mucoadhesive nanoparticles for intranasal administration using ionotropic gelation method. The developed nanoparticles were evaluated for physico-chemical properties like particle size, zeta potential, surface morphology, drug content, entrapment efficiency, in vitro drug release, mucoadhesive strength, and ex vivo permeation studies in excised porcine nasal mucosa. Optimized nanoparticle formulation (T9) was composed oil mucoadhesive agent (Chitosan 1% w/w), cross linking polymer (TPP) and topiramate 275mg, 100mg and 4% respectively. It showed particle size of 350nm, high encapsulation efficacy and strong mucoadhesive strength. In vitro drug diffusion of optimized formulation showed 95.12% release of drug after 180min. Ex-vivo permeation of drug across nasal mucosa was   88.05 % after 180min. Nasocilial toxicity studies showed optimized formulation did not damage the nasal mucosa. Thus, the intranasal administration of topiramate using chitosan can be a promising alternative for brain targeting and the treatment of epilepsy.

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