Formulation and Evaluation of Mucoadhesive in-Situ Nasal Gel of Tapentadol Hydrochloride

2021 ◽  
pp. 285-291
Author(s):  
Reema B. Gotmare ◽  
R. S. Kushwaha ◽  
Neeraj K. Sharma
Keyword(s):  
Nasal Mucosa ◽  
Prolonged Exposure ◽  
Ex Vivo ◽  
Poloxamer 407 ◽  
Peg 400 ◽  
Gelling Properties ◽  
First Pass ◽  
In Situ Nasal Gel ◽  
Histopathological Studies

Tapentadol Hydrochloride is a Tapentadol is a centrally acting analgesic. It has 33% bioavailability due to its first pass effect and hence possesses problems in the development of oral sustained release formulations. Mucoadhesive thermo reversible in-situ nasal gel of Tapentadol HCl was designed and developed to sustain its release due to the increased nasal residence time of the formulation. Poloxamer 407 (PF 127) was selected as it has excellent thermo sensitive gelling properties. HPMCK4M was added to impart mucoadhesive to the formulation, and PEG 400 was used to enhance the drug release. 32 Factorial designs were employed to assess the effect of concentration of HPMCK4M and PEG 400 on the performance of in-situ nasal gel systematically and to optimize the formulation. An optimized in-situ nasal gel was evaluated for appearance, pH, drug content, gelation temperature, mucoadhesive force, viscosity and ex-vivo permeability of drug through nasal mucosa of a goat. Additionally, this formulation was proved to be safe as histopathological studies revealed no deleterious effect on nasal mucosa of a goat after prolonged exposure of 21 days to the optimized formulation. Thus the release of Tapentadol Hydrochloride can be sustained if formulated in an in-situ nasal gel containing poloxamer 407 to achieve its prolonged action.

DEVELOPMENT AND EVALUATION OF NANOPARTICULATE BASED IN-SITU GELLING SYSTEM FOR NASAL DRUG DELIVERY OF AN ANTI-EPILEPTIC DRUG

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (09) ◽  
pp. 83-85
Author(s):  
A Ambavkar ◽  
◽  
N. Desai
Keyword(s):  
Drug Release ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Poloxamer 407 ◽  
Nasal Drug Delivery ◽  
Anti Epileptic Drug ◽  
Nanolipid Carriers ◽  
In Situ Nasal Gel

The objective of the study was to develop and evaluate nanolipid carriers based in situ gel of Carbamazepine, for brain delivery through intranasal route. The non – invasive nasal route can provide rapid delivery of drugs directly to the central nervous system by bypassing the blood brain barrier. The nanolipid carriers of carbamazepine as in situ nasal gel can prolong the drug release for control of repetitive seizures and were prepared by Phase Inversion Temperature technique. The retention of the carriers in the nasal cavity was improved by using Poloxamer 407 as thermoresponsive and Carbopol 974P as mucoadhesive gelling polymers, respectively. The developed gel was evaluated for particle size, polydispersity index, zeta potential, morphology, entrapment efficiency, mucoadhesive and thermoresponsive behaviour, in vitro drug release, ex vivo permeation and nasociliotoxicity. The gel showed sustained release over prolonged periods and was found to be non-toxic to the sheep nasal mucosa.

scholarly journals Optimization of ThermoreversibleIn SituNasal Gel of Timolol Maleate

Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Swati Jagdale ◽  
Nirupama Shewale ◽  
Bhanudas S. Kuchekar
Keyword(s):  
Drug Release ◽  
Factorial Design ◽  
Ex Vivo ◽  
Nasal Delivery ◽  
Poloxamer 407 ◽  
Timolol Maleate ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

Nasal route had shown better systemic bioavailability due to its large surface area, porous endothelial membrane, high total blood flow, and avoidance of first-pass metabolism. Timolol maleate is a beta blocker used primarily in the treatment of hypertension. Drug undergoes extensive hepatic first-pass metabolism (80%). The drug has half-life of 4 hrs. Oral bioavailability of timolol maleate is 61%. The aim of the present study was to optimize controlled releasein situnasal delivery for timolol maleate. HPMC and Poloxamer 407 were selected as polymer in formulation of thermoreversiblein situnasal gel. Optimization was carried out using 32factorial design. It was observed that formulations f1 and f4 revealed the highest % drug release, that is, 93.57% and 91.66%, respectively. Factorial design study indicated that the drug release and viscosity were most significant dependent factors.Ex vivodiffusion study through nasal mucosa indicated 67.26 ± 2.10% and 61.07 ± 2.49% drug release for f1 and f4 formulations. f1 was the optimized batch. This batch thus can act as a potential nasal delivery with enhanced bioavailability for the drug.

scholarly journals Development and Correlation between in vitro Drug Release and in vitro Permeation of Thermally Triggered Mucoadhesive in situ Nasal Gel of Repaglinide PVP K30 Complex

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Kamla Pathak ◽  
Anil Kumar ◽  
Ekta Yadav
Keyword(s):  
Ex Vivo ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Type Ii Diabetes Mellitus ◽  
Poloxamer 407 ◽  
Ex Vivo Permeation ◽  
In Situ Nasal Gel ◽  
Pvp K30

The aim of the investigation was to develop and evaluate thermoreversible in situ nasal gel formulations of repaglinide (REP) and to establish correlation between its in vitro release and ex vivo permeation profiles. The solubility of REP was enhanced by preparing solid dispersions (SDs) with hydrophilic carriers (PVP K30/ PEG 6000/ poloxamer 188) in different weight ratios. REP: PVP K30 (1:5) was selected as the optimized SD as it showed highest enhancement in solubility (405%). The optimized SD was characterized by SEM and DSC and incorporated into a blend of thermoreversible and mucoadhesive polymers (poloxamer 407 and carbopol 934 P) by cold technique to form in situ gels (F1-F6). The prepared in-situ gels were evaluated for various pharmacotechnical features and the formulation F3 exhibited least gelling time of 6.1± 0.20, good mucoadhesive property to ensure sufficient residence time at the site of application and a %CDR of 82.25%. The ex vivo permeation characteristics across goat mucosa can be summarized as CDP of 78.7%, flux = 6.80 mg/cm2/h; permeability coefficient of 2.02 mg/h and zero order kinetics. On correlating the CDR profile of F3 with that of its CDP profile, a R2 value of 0.991 (slope= 0.921) was observed. The value of slope approximating one, suggested that almost entire amount of drug released from F3 was capable of permeating across the nasal mucosa, ex-vivo indicating that in-situ nasal gels of REP for systemic action can be successfully developed for the management non-insulin dependent type-II diabetes mellitus.

scholarly journals COMBINATION OF METFORMIN AND CURCUMIN THERMOREVERSIBLE NASAL IN SITU GEL FORMULATION AND IN VITRO-EX VIVO EVALUATION FOR DIABETES-INDUCED ALZHEIMER’S DISEASE

2021 ◽  
Vol 12 (6) ◽  
pp. 26-34
Author(s):  
Anuja Anku ◽  
K. Abbulu ◽  
Sowjanya Battu ◽  
Kalam Marryswarnalatha ◽  
T. Sri Lakshmi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nasal Mucosa ◽  
Ex Vivo ◽  
In Situ Gel ◽  
Mucoadhesive Polymers ◽  
Carbopol 940 ◽  
Histopathological Studies

The present research was focused to prepare the formulation containing combination of Metformin and Curcumin to control diabetes-induced Alzheimer’s in elderly population with the utilization of Poloxamer P188 (8%), a thermoreversible gelling polymer, and mucoadhesive polymers such as Carbopol 940, Sodium alginate and HPMC K100 in varying concentrations (0.5%, 1%, 1.5% and 2% respectively) to improve the absorption of drugs by increasing the contact time with nasal mucosa. The in situ gel was prepared by cold method and administered via nasal route to deliver the drug directly to CNS by bypassing BBB and to improve patient compliance, nasal bioavailability of drugs by cumulative its nasal retention time in nasal mucosa. Total 12 nasal in situ gels were prepared and evaluated for in vitro studies and ex vivo drug diffusion studies (goat nasal mucosa) and results were found to be satisfactory. Moreover, histopathological studies revealed that the preparation was safe to be used on nasal mucosa of goat. The prepared nasal in situ gel is an effective alternative to conventional method and can be used to treat diabetes-induced Alzheimer’s disease.

scholarly journals Development of In Situ Gelling Meloxicam-Human Serum Albumin Nanoparticle Formulation for Nose-to-Brain Application

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 646
Author(s):  
Gábor Katona ◽  
Bence Sipos ◽  
Mária Budai-Szűcs ◽  
György Tibor Balogh ◽  
Szilvia Veszelka ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Nasal Mucosa ◽  
Drug Absorption ◽  
Cell Damage ◽  
Lipid Fraction ◽  
Poloxamer 407 ◽  
Nasal Drug Delivery

The aim of this study was to develop an intranasal in situ thermo-gelling meloxicam-human serum albumin (MEL-HSA) nanoparticulate formulation applying poloxamer 407 (P407), which can be administered in liquid state into the nostril, and to increase the resistance of the formulation against mucociliary clearance by sol-gel transition on the nasal mucosa, as well as to improve drug absorption. Nanoparticle characterization showed that formulations containing 12–15% w/w P407 met the requirements of intranasal administration. The Z-average (in the range of 180–304 nm), the narrow polydispersity index (PdI, from 0.193 to 0.328), the zeta potential (between −9.4 and −7.0 mV) and the hypotonic osmolality (200–278 mOsmol/L) of MEL-HSA nanoparticles predict enhanced drug absorption through the nasal mucosa. Based on the rheological, muco-adhesion, drug release and permeability studies, the 14% w/w P407 containing formulation (MEL-HSA-P14%) was considered as the optimized formulation, which allows enhanced permeability of MEL through blood–brain barrier-specific lipid fraction. Cell line studies showed no cell damage after 1-h treatment with MEL-HSA-P14% on RPMI 2650 human endothelial cells’ moreover, enhanced permeation (four-fold) of MEL from MEL-HSA-P14% was observed in comparison to pure MEL. Overall, MEL-HSA-P14% can be promising for overcoming the challenges of nasal drug delivery.

In Situ Gels of Acylovir Nanoemulsions For Improved Delivery to The Eye

2021 ◽  
Vol 11 ◽  
Author(s):  
Manza M. Priyanka ◽  
Shinde A. Ujwala ◽  
Sheth M. Kalyani ◽  
Namita Desai
Keyword(s):  
Animal Studies ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Corneal Stroma ◽  
Class Iii ◽  
Ophthalmic Delivery ◽  
Histopathological Studies

Background: Acyclovir, BCS Class III drug is commercially available as 3 % w/w eye ointment for multiple applications. Acyclovir nanoemulsions can be proposed to reduce dose because of improved permeation characteristics. Further, the development of in situ ophthalmic gels can be advantageous to reduce the number of applications due to increased mucoadhesion and sustaining effect. Objective: The purpose of this study was the development and evaluation of nanoemulsions based in situ gels of Acyclovir (1% w/w) as potential ophthalmic delivery systems. Methods: Nanoemulsions of Acyclovir were developed by Phase Inversion Temperature method using Capmul MCM, stearyl amine and Kolliphor RH 40 as liquid lipid, charge inducer and surfactant, respectively selected on the basis of Acyclovir solubility studies in the oil phase and emulsification ability of surfactants. These nanoemulsions were further developed into in situ ophthalmic gels using gellan gum and Methocel K4M. Results: The developed gels showed a sustained effect in vitro release studies and improved goat corneal permeation in ex vivo studies when compared to marketed ointment. HET-CAM studies concluded the absence of irritation potential, while in vivo irritation study in Wistar rats showed the absence of erythema and swelling of eyes after visual inspection for 72 hours. Histopathological studies on isolated rat corneas showed no abnormalities in anterior corneal epithelium and corneal stroma without any epithelial hyperplasia. Acyclovir nanoemulsions based in situ ophthalmic gel showed increased corneal deposition and permeation in rat eyes. Conclusion: The improved potential of developed ophthalmic gels was proven due to the reduced frequency of application compared to the marketed ointment in animal studies.

scholarly journals Cyclosporine Lipid Nanocapsules as Thermoresponsive Gel for Dry Eye Management: Promising Corneal Mucoadhesion, Biodistribution and Preclinical Efficacy in Rabbits

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 360
Author(s):  
Lubna M. Eldesouky ◽  
Riham M. El-Moslemany ◽  
Alyaa A. Ramadan ◽  
Mahmoud H. Morsi ◽  
Nawal M. Khalafallah
Keyword(s):  
Dry Eye ◽  
Ex Vivo ◽  
Histopathological Examination ◽  
Entrapment Efficiency ◽  
Poloxamer 407 ◽  
Lipid Nanocapsules ◽  
Ocular Irritation ◽  
Schirmer Tear Test

An ophthalmic cyclosporine (CsA) formulation based on Lipid nanocapsules (LNC) was developed for dry eye management, aiming to provide targeting to ocular tissues with long-term drug levels and maximum tolerability. CsA-LNC were of small particle size (41.9 ± 4.0 nm), narrow size distribution (PdI ≤ 0.1), and high entrapment efficiency (above 98%). Chitosan (C) was added to impart positive charge. CsA-LNC were prepared as in-situ gels using poloxamer 407 (P). Ex vivo mucoadhesive strength was evaluated using bovine cornea, while in vivo corneal biodistribution (using fluorescent DiI), efficacy in dry eye using Schirmer tear test (STT), and ocular irritation using Draize test were studied in rabbits compared to marketed ophthalmic CsA nanoemulsion (CsA-NE) and CsA in castor oil. LNC incorporation in in-situ gels resulted in an increase in mucoadhesion, and stronger fluorescence in corneal layers seen by confocal microscopy, compared to the other tested formulations. Rate of recovery (days required to restore corneal baseline hydration level) assessed over 10 days, showed that CsA-LNC formulations produced complete recovery by day 7 comparable to CsA-NE. No Ocular irritation was observed by visual and histopathological examination. Based on data generated, CsA-LNC-CP in-situ gel proved to be a promising effective nonirritant CsA ophthalmic formulation for dry eye management.

scholarly journals Formulation and Evaluation of Sustained Release Sumatriptan Mucoadhesive Intranasal in-Situ Gel

2019 ◽  
Vol 28 (2) ◽  
pp. 95-104
Author(s):  
Hussein K. Alkufi ◽  
Hanan J. Kassab
Keyword(s):  
Drug Release ◽  
Ex Vivo ◽  
Poloxamer 407 ◽  
Gelation Temperature ◽  
In Vitro Drug Release ◽  
In Situ Gel ◽  
Ex Vivo Permeation ◽  
Ex Vivo Permeation Study

     Objective: The purpose of this study to develop and optimize nasal mucoadhesive in situ gel IG of sumatriptan ST (serotonin agonist) to enhance nasal residence time for migraine management.      Method: Cold method was used to prepare ST nasal in-situ gel, using thermosensitive polymers (poloxamer 407  and/or poloxamer 188) with a mucoadhesive polymer (hyaluronic acid HA) which were examined for gelation temperature and gelation time, pH, drug content, gel strength, spreadability, mucoadhesive force determination, viscosity,  in-vitro drug release, and the selected formula was subjected to ex-vivo permeation study and histological evaluation of the sheep mucosal tissue after application.     Results: The results showed that the formula IG7 prepared from poloxamer 407(19%), poloxamer188 (4%) and HA (0.5%)   had an optimum gelation temperature (32.66±1.52°C), gel  strength (43.66± 1.52 sec),  mucoadhesive force (8067.93± 746.45dyne\cm2), in-vitro drug release (95.98%) over 6hr, ex-vivo permeation study release (89.6%)  during the 6 h. study with no  histological or pathological change in the nasal sheep tissue.     Conclusion: The ease of administration via a nasal drop of ST coupled with less frequent administration and prolong drug release, will enhance patient compliance.

scholarly journals In situ Intranasal Delivery Systems: Application Prospects and Main Pharmaceutical Aspects of Development (Review)

2021 ◽  
Vol 10 (4) ◽  
pp. 54-63
Author(s):  
E. O. Bakhrushina ◽  
N. B. Demina ◽  
M. M. Shumkova ◽  
P. S. Rodyuk ◽  
D. S. Shulikina ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Delivery Systems ◽  
Genetically Engineered ◽  
Biological Molecules ◽  
Poloxamer 407 ◽  
Prolonged Release ◽  
Preclinical Studies ◽  
Intranasal Delivery

Introduction. Intranasal delivery of in situ gel-forming systems is a complex but promising direction. Due to the high cost of developing a new chemical object or genetically engineered modification of biological molecules, pharmaceutical companies are focusing on developing technologies for new delivery systems for existing active pharmaceutical ingredients to improve their effectiveness and bioavailability. In situ systems for intranasal delivery, due to increased viscosity and mucoadhesion to the nasal mucosa, allow overcoming mucociliary clearance and ensuring complete absorption and prolonged release of drugs.Text. The article discusses the main advantages of intranasal in situ delivery systems shown in preclinical studies, as well as approaches to the technology of obtaining and standardization of these systems. The results of scientific research in this field over the past 15 years are summarized, the most promising polymers for creating thermoreversible and pH-sensitive compositions are identified, and modern methods for evaluating the sol-gel transition in situ are analyzed.Conclusion. The use of in situ systems for intranasal administration allows providing a high targeting of the delivery of synthetic and biological molecules to the brain. Currently, numerous pharmacokinetic and pharmacodynamic preclinical studies confirm the effectiveness of such systems, as well as their safety. Thermoreversible commercially available and directionally synthesized polymers (poloxamer 407, PLGA, NIPAAm, etc.), as well as chitosan, remain the most popular for the design of in situ delivery systems. In vitro and ex vivo methods with mucosa and artificial nasal fluid are widely used to assess the parameters of in situ gelation, but to increase the reproducibility of the methods and improve the correlation in vitro/in vivo, it is recommended to conduct modeling of the nasal cavity. Developing the technology and methods of screening of intranasal reversible systems will help to get closer to clinical trials and the entry of these delivery systems into the global pharmaceutical market.

scholarly journals FORMULATION AND EVALUATION OF IN SITU MUCOADHESIVE THERMOREVERSIBLE NASAL GEL OF SERTRALINE HYDROCHLORIDE

2019 ◽  
pp. 195-202
Author(s):  
DIKSHA SHARMA ◽  
SHAWETA AGARAWAL
Keyword(s):  
Drug Release ◽  
Biological Membrane ◽  
Poloxamer 407 ◽  
Compatibility Study ◽  
In Vitro Drug Release ◽  
In Situ Gel ◽  
Sertraline Hydrochloride ◽  
In Situ Nasal Gel

Objective: The objective of the study was to aiming to formulate and evaluate temperature based in situ nasal gel of sertraline HCL. Materials and Methods: Preformulation studies of sertraline hydrochloride including tests for identification, solubility studies, Fourier-transformer infrared (FTIR) spectroscopy, melting point determination, and other studies were carried out and compared with the specification as per literature. The solubility of sertraline hydrochloride was determined in different solvents such as in distilled water, ethanol, acetone, isopropyl alcohol, and 2-propanol. Each value for solubility was determined in triplicate and average values were reported. The drug excipient compatibility study was determined by FTIR. Thermal analysis was performed using a differential scanning calorimetric equipped with a computerized data station. The UV spectrum of sertraline hydrochloride was obtained using UV JascV630. The in situ gel formulation was prepared by changing the concentration and using only one polymer (Carbopol 934) has been used at the same concentration. Mucoadhesive strength and in vitro permeation study were determined using gout nasal mucosal membrane, whereas in vitro drug release study was carried out using diffusion cell through egg membrane as a biological membrane. The stability studies were conducted according to ICH guidelines. Results: The FTIR studies of formulation show no interaction between drug and excipient. In situ gel was prepared using Carbopol 934 and Poloxamer 407 to improve its adhesion property. The optimized formulation (F6) was transparent and clear in appearance with 101.15% drug content. The sol-gel transformation of in situ gel was found at temperature 34.92°C with immediate gelation property. The in vitro drug release of optimized formulation was found 95.80% drug release in 8 h. Formulations F4 and F6 showed immediate gelation within 60 s and remained stable for an extended period. All the formulations were liquid at room temperature and underwent rapid gelation on contact with simulated nasal fluid. Conclusion: The results concluded that the formulations of in situ nasal gel showing to improve the bioavailability through its longer residence time and ability to sustain drug release.

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