scholarly journals Design and Optimization of Thermo-reversible Nasal in situ Gel of Atomoxetine Hydrochloride Using Taguchi Orthogonal Array Design

2019 ◽  
Vol 18 (2) ◽  
pp. 183-193 ◽  
Author(s):  
PK Lakshmi ◽  
K Harini
Keyword(s):  
Drug Release ◽  
Residence Time ◽  
Poloxamer 407 ◽  
Release Mechanism ◽  
Gelation Temperature ◽  
In Situ Gel ◽  
Design And Optimization ◽  
Mucoadhesive Polymers ◽  
Carbopol 934P

The present investigation was aimed to develop a thermo-reversible nasal in situ gel of atomoxetine hydrochloride (AH) with reduced nasal muco-ciliary clearance in order to improve residence time and targeting the brain through nasal mucosa for the treatment of attention-deficit hyperactivity disorder (ADHD). In situ gel formulations were prepared using different concentrations of the thermo-gelling poloxamer 407 and mucoadhesive polymers. Temperature-triggered ionic gelation is the mechanism involved. Taguchi L9 OA experimental design was employed for the optimization of the effect of independent variables (Poloxamer 407 and Carbopol 934P) on the response (gelation temperature). In situ gel formulation F4 having 20% poloxamer 407 and 0.3% carbopol 934P and formulation F6 having 20% poloxamer 407 and 0.2% HPMC K100 were optimized based on evaluation parameters. The gelation temperature of F4 and F6 was found to be 37°C ± 0.4 and 37°C ± 0.2, drug content 98.34 and 98.33% and drug release was 83.18, 82.4% in 4 hrs with a flux of 436.9 and 428.1 μg.cm2/hr, respectively. The release pattern of drug followed first-order kinetics with Higuchi release mechanism. The value of ‘n’ from Korsemeyer equation indicated the anomalous diffusional drug release. This study concluded that in situ gel enhanced the nasal residence time and thus may improve the bioavailability of the drug through nasal route by avoiding first pass metabolism Dhaka Univ. J. Pharm. Sci. 18(2): 183-193, 2019 (December)

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 Micro spect in vivo bio-distribution study of azithromycin ophthalmic in situ gel

2020 ◽  
Vol 11 (3) ◽  
pp. 4546-4554
Author(s):  
Manish Wani ◽  
Swati Jagdale ◽  
Vishal Bhujbal ◽  
Akshay Baheti ◽  
Ashwin Kuchekar
Keyword(s):  
Drug Release ◽  
Residence Time ◽  
Polymer Concentration ◽  
Experimental Studies ◽  
Poloxamer 407 ◽  
Gelling Agent ◽  
In Situ Gel ◽  
Biodistribution Studies

Azithromycin (AZT) is a broad-spectrum antibiotic and is found in ocular tissues when administered systemically. AZT inhibits RNA-dependent protein synthesis and hence has effective bactericidal capability against Staphylococcus aureus, Pseudomonas aeruginosa, which are the primary causative organisms for bacterial infection. In situ ophthalmic gels are systems which undergo a sol-to-gel transformation when instilled in eyes. In situ gels overcome the shortcoming of ophthalmic drops as they get washed out and diluted due to tear fluid. The aim and objective of present study was to formulate in situ ophthalmic gelling systems of Azt and determine in vivo ocular residence time in rat eyes of Tc99 labelled Azt by Micro SPECT. The in situ gel was formulated using Poloxamer 407, which is a temperature-induced gelling agent and HPMC K4M, which is known to increases mucosal adhesivity and enhance viscosity to facilitate sustained release of drug. The formulations developed were evaluated for pH, clarity, viscosity, gelling capacity and % drug release. The selected formulation was subjected to isotonicity and In Vivo Bio-distribution studies. Experimental studies on compatibility showed no interaction between polymers and AZT. AZT was found soluble in PB6.8. All formulations were found clear immediately after preparation and after sterilization & pH after gelation was satisfactorily in the range of 6 to 7. Viscosity and Gelation capacity of in situ gel increased with increase in polymer concentration. Formulations F2 showed desired results w.r.t viscosity, gelation capacity, drug release. In Vivo Biodistribution studies of Tc99 labelled AZT by Micro SPECT showed there was a significant increase in ocular residence time of in situ gel when compared with Tc99 labelled marketed solutions.

scholarly journals DEVELOPMENT AND EVALUATION OF AN IN SITU THERMOGELLING SYSTEM OF OFLOXACIN FOR CONTROLLED OCULAR DELIVERY

2019 ◽  
pp. 567-570 ◽  
Author(s):  
ANANTH PRABHU ◽  
MARINA KOLAND
Keyword(s):  
Drug Release ◽  
In Vitro Release ◽  
Methyl Cellulose ◽  
Poloxamer 407 ◽  
Temperature Sensitive ◽  
Gelation Temperature ◽  
Mucoadhesive Polymers ◽  
In Situ Gelling

Objective: The purpose of this study was to develop an in situ ocular gel of ofloxacin which aimed to prolong corneal residence time while controlling drug release. Method: In situ gelling solutions were prepared from Poloxamer 407, a temperature-sensitive gelling polymer and to which, mucoadhesive polymers such as hydroxypropyl methyl cellulose 15 cps and polyvinyl alcohol (PVA) were included to provide corneal adhesion. Drug incorporated gels were prepared and evaluated for their appearance, pH, gelation temperature, and in vitro drug release studies. Results: Incorporation of the drug into the formulation increased the gelation temperature while the addition of mucoadhesive polymers decreased the gelation temperature. Increasing the concentration of bio-adhesive polymers retarded the release of ofloxacin from the poloxamer solutions and drug release was sustained over a period of 9 h. PVA had no significant effect on the gelation temperature and could not sustain the drug release for a longer duration. The in vitro release profiles of the drug from all the formulations could be best expressed by Higuchi’s equation which indicated that gels followed matrix diffusion process and drug release from gel formulations followed first-order process. Conclusion: The results showed that the developed system would be promising in the treatment of ocular infections with the combined advantages of ease of administration, the accuracy of dosing, increased bioavailability, and prolonged retention time.

scholarly journals Development of a Cyclodextrin-Based Mucoadhesive-Thermosensitive In Situ Gel for Clonazepam Intranasal Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 969
Author(s):  
Marzia Cirri ◽  
Francesca Maestrelli ◽  
Giulia Nerli ◽  
Natascia Mennini ◽  
Mario D’Ambrosio ◽  
...  
Keyword(s):  
Drug Release ◽  
Gelation Time ◽  
Sodium Hyaluronate ◽  
Controlled Drug Release ◽  
Intranasal Delivery ◽  
Gelation Temperature ◽  
In Situ Gel ◽  
Permeation Studies ◽  
The One

A thermosensitive, mucoadhesive in-situ gel for clonazepam (CLZ) intranasal delivery was developed, which aimed to achieve prolonged in-situ residence and controlled drug release, overcoming problems associated with its oral or parenteral administration. Poloxamer was selected as a thermosensitive polymer and chitosan glutamate and sodium hyaluronate as mucoadhesive and permeation enhancer. Moreover, randomly methylated β-Cyclodextrin (RAMEB) was used to improve the low drug solubility. A screening DoE was applied for a systematic examination of the effect of varying the formulation components proportions on gelation temperature, gelation time and pH. Drug-loaded gels at different clonazepam-RAMEB concentrations were then prepared and characterized for gelation temperature, gelation time, gel strength, mucoadhesive strength, mucoadhesion time, and drug release properties. All formulations showed suitable gelation temperature (29–30.5 °C) and time (50–65 s), but the one with the highest drug-RAMEB concentration showed the best mucoadhesive strength, longest mucoadhesion time (6 h), and greatest release rate. Therefore, it was selected for cytotoxicity and permeation studies through Caco-2 cells, compared with an analogous formulation without RAMEB and a drug solution. Both gels were significantly more effective than the solution. However, RAMEB was essential not only to promote drug release, but also to reduce drug cytotoxicity and further improve its permeability.

Development of In Situ Gel for Oral Application

2014 ◽  
Vol 1060 ◽  
pp. 66-69
Author(s):  
Suwannee Panomsuk ◽  
Pimchanok Nakprasong ◽  
Suthi On Tanpichai ◽  
Sasithorn Chin-Aramrungruang
Keyword(s):  
Drug Release ◽  
Buccal Mucosa ◽  
Sol Gel ◽  
Gel Strength ◽  
Medical Product ◽  
Poloxamer 407 ◽  
In Situ Gel ◽  
Model Drug ◽  
Gel Temperature

In situ gel, a new concept of medical product for oral applications was developed using Poloxamer 407 (P) and Carbopol 934 (C) which are thermo-and pH-sensitive sol-gel polymers, respectively. The formulations were evaluated for the physical appearance, pH, viscosity, sol-gel temperature, gel strength and buccal mucoadhesive (adhesion to porcine buccal mucosa). Benzalkonium chloride (BzCl) 0.1% w/v was added in the suitable formulations as a model drug. Formulations containing 20% P (pH = 7.1) and 20% P + 0.6% C (pH = 5.0) showed good physical appearances which turned to gels in buccal conditions. Their mucoadhesive force to porcine buccal mucosa were higher than formulations containing 10 and 15 % P(p<0.05). The present of 0.6 % C in the formulation did not affect gel strength but tended to increase mucoadhesive properties. The release of BzCl from the formulations was performed using Franz diffusion cell at 37°C for 1 hour. There were no different in drug release from both formulations(p<0.05), the amount of drug release was 11.7% ± 4.4 and 10.9% ± 0.8, respectively. In conclusion, formulation containing 20% P and 0.6% C has revealed the most suitable properties as in situ gel for buccal mucosa applications, the release of BzCl was 10.9% ± 0.8 within 1 hour.

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.

scholarly journals FORMULATION AND EVALUATION OF IN-SITU GEL CONTAINING LINEZOLID IN THE TREATMENT OF PERIODONTITIS

2021 ◽  
pp. 79-86
Author(s):  
INAYATHULLA . ◽  
PRAKASH GOUDANAVAR ◽  
MOHAMMAD ALI ◽  
SHAHID UD DIN WANI ◽  
NAGARAJA SREEHARSHA
Keyword(s):  
Drug Release ◽  
Polymer Concentration ◽  
Hydroxypropyl Methylcellulose ◽  
In Vitro Release ◽  
In Situ Gel ◽  
Diffusion Controlled ◽  
Gelling Time ◽  
Carbopol 934P

Objective: The intent to prepare and evaluate Linezolid in-situ gel in the treatment of periodontitis. Methods: pH-sensitive in-situ gel was formed by the cold method using a varying concentration of the drug, carbopol 934P and hydroxypropyl methylcellulose (HPMC) and carbopol 934P and sodium carboxy methylcellulose (CMC) (1:1,1:1.5,1:2,1:2.5). An optimized batch was selected based on gelling time and gelling capacity. The prepared in-situ gels were evaluated for appearance, pH, gelling capacity, viscosity, in vitro release studies, rheological studies, and finally, was subjected to drug content estimation and antibacterial activity test. Results: FTIR study shows drug and physical mixture were compatible with each other. The rheology of formulated in-situ gel exhibited a pseudoplastic flow pattern. this may be because when polymer concentration was increased the prepared formulations become more viscous and in turn delayed the drug release and from the prepared formulation, LF4 and SF4 have polymer concentrations i. e, 0.9% carbopol and sodium CMC showed drug release up to 12 h. Conclusion: When carbopol is appropriately mixed with other suitable polymers it forms an in-situ gel-forming system that was substantiated by the property to transform into stiff gels when the pH is increased. The in-situ gel was prepared using a combination of carbopol-HPMC and carbopol-Na CMC The formulations LF1 to SF4 showed high linearity (R2 = 0.490-0.682), indicating that the drug was released from the prepared in-situ gel by the diffusion-controlled mechanism. Thus, the formulation of batches LF4 and SF4 containing carbopol: HPMC and carbopol: NaCMC in 1:2 ratios were considered as optimum formulation based on optimum viscosity, gelling capacity and to extend the in vitro drug release.

scholarly journals IN VITRO DRUG RELEASE STUDY OF CHLORAMPHENICOL IN SITU GEL WITH BASES MIXTURE OF POLOXAMER 407 AND HPMC BY OPTIMIZATION WITH FACTORIAL DESIGN

2021 ◽  
pp. 116-123
Author(s):  
INSAN SUNAN KURNIAWANSYAH ◽  
TAOFIK RUSDIANA ◽  
HURIYATUS TSANIYAH ◽  
HANDRIAN RAMOKO ◽  
HABIBAH A. WAHAB ◽  
...  
Keyword(s):  
Drug Release ◽  
Factorial Design ◽  
Hydroxypropyl Methylcellulose ◽  
Poloxamer 407 ◽  
In Vitro Dissolution ◽  
In Situ Gel ◽  
Vitro Assay ◽  
Cumulative Amount

Objective: The objective of this study was to find the best base mixture composition (poloxamer 407 and HPMC) of chloramphenicol in situ gel formula based on in vitro property (Cumulative amount of drug release). Methods: The in vitro diffusion of chloramphenicol in situ gel study was carried out using franz diffusion cells to know the effect of the Critical Process Parameters (CPPs) as independent variables (poloxamer 407 and hydroxypropyl methylcellulose (HPMC)) on the Critical Quality Attribute (CQA) as dependent variable (cumulative amount of drug release) with 22 factorial design. Results: 22 factorial design of chloramphenicol in situ gel yielded 4 variations of poloxamer 407 and HPMC bases component in %w/v as follows, F1 (5:0.45), F2 (10:0.45) F3 (5:1) and F4 (10:1). The amount of drug release results from in vitro dissolution assay were 30.60% (F1), 45.64% (F2), 58.30% (F3), and 22.50%) (F4). Conclusion: Formula 3 (F3) was considered as the best formula component in terms of in vitro assay of chloramphenicol in situ gel with a desirability value of 0.58.

Synthesis of hybrid polymer blend nanoparticles and incorporation into in situ gel foam spray for controlled release therapy using a versatile synthetic purine nucleoside analogue antiviral drug

RSC Advances ◽  
2015 ◽  
Vol 5 (17) ◽  
pp. 12956-12973 ◽  
Author(s):  
Durai Ramyadevi ◽  
Kalpoondi Sekar Rajan
Keyword(s):  
Controlled Release ◽  
Drug Release ◽  
Nucleoside Analogue ◽  
Antiviral Drug ◽  
Release Mechanism ◽  
Hybrid Polymer ◽  
In Situ Gel ◽  
Drug Release Mechanism ◽  
Physical Interactions

Antiviral drug loaded nanoparticles is incorporated intoin situgel for controlled release therapy. Chemical and physical interactions of drug and polymers in the system influenced their characteristics and drug release mechanism.

scholarly journals DEVELOPMENT AND CHARACTERIZATION OF IN SITU GEL OF XANTHAN GUM FOR OPHTHALMIC FORMULATION CONTAINING BRIMONIDINE TARTRATE

2018 ◽  
Vol 11 (7) ◽  
pp. 277 ◽  
Author(s):  
Vazir Ashfaq Ahmed ◽  
Divakar Goli
Keyword(s):  
Drug Release ◽  
Xanthan Gum ◽  
Gelation Time ◽  
Gel Strength ◽  
Eye Drops ◽  
In Situ Gel ◽  
23 Factorial Design ◽  
Brimonidine Tartrate

Objective: The goal of this study was to develop and characterize an ion-activated in situ gel-forming brimonidine tartrate, solution eye drops containing xanthan gum as a mucoadhesive polymer.Method: Sol-gel formulation was prepared using gellan gum as an ion-activated gel-forming polymer, xanthan gum as mucoadhesive agent, and hydroxypropyl methyl cellulose (HPMC E50LV) as release retardant polymer. Phenylethyl alcohol is used as preservatives in borate buffer. The 23 factorial design was employed to optimize the formulation considering the concentration of gelrite, xanthan gum and HPMC as independent variables, gelation time, gel strength, and mucoadhesive force (N). Gelation time , gel strength, mucoadhesive force (N), viscosity (cP) and in vitro percentage drug release were chosen as dependent variables. The formulation was characteristics for pH, clarity, isotonicity, sterility, rheological behavior, and in vitro drug release, ocular irritation, and ocular visualization.Result: Based on desirability index of responses, the formulation containing a concentration of gelrite (0.4%), xanthan gum (0.21%), and HPMC (HPMC E50 (0.24%) was found to be the optimized formulation concentration developed by 23 factorial design. The solution eye drops resulted in an in situ phase change to gel-state when mixed with simulated tear fluid. The gel formation was also confirmed by viscoelastic measurements. Drug release from the gel followed non-fickian mechanism with 88% of drug released in 10 h, thus increased the residence time of the drug.Conclusion: An in situ gelling system is a valuable alternative to the conventional system with added benefits of sustained drug release which may ultimately result in improved patient compliance.

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