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.

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.

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 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 IN-SITU GEL CONTAINING CIPROFLOXACIN HYDROCHLORIDE IN THE TREATMENT OF PERIODONTITIS.

2017 ◽  
Vol 10 (6) ◽  
pp. 154 ◽  
Author(s):  
Gorle Ashish ◽  
Yadav Rahul ◽  
Rathod Mukesh ◽  
Mali Prakash
Keyword(s):  
Drug Release ◽  
Gelation Time ◽  
Gellan Gum ◽  
Pluronic F127 ◽  
Periodontal Pocket ◽  
Content Uniformity ◽  
In Situ Gel ◽  
Wide Range

Objective: The present study describes the use of in-situ gel in periodontal drug delivery systems which contains gellan gum (0.4–0.6% w/v), pluronic F127 (14, 15 and 16% w/v), and drug Ciprofloxacin HCl (0.1% w/v). Number of peoples around the world suffered from dental problem and ultimate fear is tooth loss hence in-situ gelling system was designed for the treatment of periodontal diseases. The therapeutic efficacy of drug can be greatly improved by prolonging its contact time.Methods: Formulations were developed by simple solution method. Each formulation was characterized in terms of in gelling strength, viscosity, rheology, content uniformity, in vitro drug release, and syringeability.Results: In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.6% w/v of gellan gum and 14% w/v of pluronic F127 exhibited superior physical characteristics. The formulation stored at 4˚C before application, which is syringeable through 21 gauge needle.Conclusion: This formulation was made to inject directly in to periodontal pocket where it immediately converts in to gel form at body temperature. 

scholarly journals Chemiluminescence-initiated and in situ-enhanced photoisomerization for tissue-depth-independent photo-controlled drug release

2019 ◽  
Vol 10 (5) ◽  
pp. 1401-1409 ◽  
Author(s):  
Yufu Tang ◽  
Xiaomei Lu ◽  
Chao Yin ◽  
Hui Zhao ◽  
Wenbo Hu ◽  
...  
Keyword(s):  
Drug Release ◽  
Penetration Depth ◽  
Controlled Drug Release ◽  
Tissue Penetration

Tissue-penetration-depth-independent self-luminescence is highly expected to perform photoisomerization-related bioapplications in vivo to overcome the limitation of shallow tissue-penetration from external photoexcitation.

scholarly journals IN SITU GEL AS PLATFORM FOR KETOCONAZOLE SLOW RELEASE DOSAGE FORM

2018 ◽  
Vol 10 (5) ◽  
pp. 76
Author(s):  
Methaq Hamad Sabar ◽  
Iman Sabah Jaafar ◽  
Masar Basim Mohsin Mohamed
Keyword(s):  
Drug Release ◽  
Guar Gum ◽  
Polymer Concentration ◽  
Hydroxypropyl Methylcellulose ◽  
In Vitro Release ◽  
High Viscosity ◽  
In Situ Gel ◽  
Alginate Concentration

Objective: The aim of this study was to formulate ketoconazole (keto) as oral floating in situ gel to slow the release of keto in the stomach.Methods: Sodium alginate (Na alginate) was used as a primary polymer in the preparation of the in situ gel and was supported by the following polymers: guar gum (GG), hydroxypropyl methylcellulose (HPMC) K4M, K15M and carbapol 940 as viscosity enhancing agents. As a consequence, and to complete the gelation process of above formulations was by adding the calcium carbonate (CaCO3). The in situ gels were investigated by the following tests: floating lag time, floating duration, viscosity, drug content, in vitro gelling studies and in vitro release study.Results: The study showed that the faster release was obtained with F1 which contained Na alginate alone. Additionally, reduction in Na alginate concentration resulted in significant increase in drug release. It was also noted that the increase in GG (viscosity enhancing polymer) concentration resulted in non-significant decrease in percent drug release and the reduction in CaCO3 concentration led to significant increase in drug release. Moreover, the release of drug was also affected by grade of viscosity enhancing polymer, the faster release was observed with the formula which contained a polymer of low viscosity (HPMC K4M) and an opposite result was with the high viscosity polymer (HPMCK15M).Conclusion: This study showed the formulation of Na alginate with GG and CaCO3, led to gain floating in situ gel and a sustained release of keto. 

scholarly journals DESIGN, OPTIMIZATION & IN-VITRO EVALUATION OF SODIUM ALGINATE BASED IN-SITU GEL OF RANITIDINE HYDROCHLORIDE IN ULCER TREATMENT

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sanket Kumar ◽  
Mahesh Singh ◽  
Babulal Patel
Keyword(s):  
Peptic Ulcer ◽  
Drug Release ◽  
Sodium Alginate ◽  
Gelling Agent ◽  
Cross Linking ◽  
Physical Interaction ◽  
In Situ Gel ◽  
Ranitidine Hydrochloride ◽  
Ulcer Treatment

Peptic ulcer, it is the most common type of stomach disease, according to the American Gastroenterology Association. “We know that ulcers occur because there has been a disruption in the balance of factors that injure the digestive tract and those factors that protect it from injury,” The present investigation deal with the formulation, optimization and evaluation of sodium alginate based in situ gel of ranitidine hydrochloride (R-HCl) in ulcer treatment. The in-situ formulation are homogenous liquid when administration orally and become gel at the contact site. The evaluation of the formulation is dependent upon accurate results obtained by analytical method used during the study. Accurate results require the use of standard and a calibration procedure. Hence, standard plots of Ranitidine hydrochloride were prepared in (0.1N HCL, pH 1.2) solutions. Two, sodium alginate and calcium carbonate used as a polymer and cross-linking agent respectively in the formulation of in-situ gel. From the IR studies it may be concluded that the drug and carriers used undergo physical interaction there is no chemical change, and thus the gelling agent, cross-linking agent and other excipient is suitable for formulation of in-situ gel of ranitidine hydrochloride. Indicate that the formulation, DKF9 which was prepared by the Sodium alginate (2 gm) with Ranitidine Hydrochloride showed minimum drug release (sustained drug release) after 8 hrs. It can be concluded that the In-situ gel was beneficial for delivering the drug which needs sustained release to achieve the slow action. Keywords: In-situ gel, Peptic Ulcer, Ranitidine Hydrochloride (R-HCl), Sodium alginate.

Nanoparticles laden In situ gel for sustained drug release after topical ocular administration

2020 ◽  
Vol 57 ◽  
pp. 101736
Author(s):  
Upadhyay Shivam U ◽  
Chavan Siddhi K ◽  
Gajjar Devarshi U ◽  
Upadhyay Umeshkumar M ◽  
Patel Jayvadan K
Keyword(s):  
Drug Release ◽  
Sustained Drug Release ◽  
In Situ Gel

scholarly journals FORMULATION, OPTIMIZATION, AND EVALUATION OF IN-SITU GEL OF MOXIFLOXACIN HYDROCHLORIDE FOR OPHTHALMIC DRUG DELIVERY

2019 ◽  
pp. 147-158
Author(s):  
Chitra Gupta ◽  
VIJAY JUYAL ◽  
Upendra Nagaich
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Influential Factors ◽  
Drug Formulation ◽  
In Situ Gel ◽  
Formulation Optimization ◽  
Ophthalmic Drug Delivery ◽  
Ophthalmic Drug

Objective: The present study emphasizes the synthesis, optimization, and evaluation of ocular in-situ gel for ophthalmic drug delivery against conjunctivitis. Methods: Pre-formulation studies on the drug and polymers were carried out, which included the study of various physicochemical properties of the drug and drug-polymer compatibility studies. The 12 different formulations were further pre-optimised by Taguchi method for determining the number of influential factors. Furthermore, the formulation optimization was done by using ‘Box–Behnken’ design (BBD) (Design expert 10 software) for assessing the effect of formulation variables on product characteristics viz. viscosity, gelation temperature (GT), and mean release time (MRT). About 13 suggested runs of the experiment were carried out and formulations were optimised. Finally, three batches of the optimised formulation were prepared and evaluated for in vitro drug release, isotonicity of formulation, anti-microbial potential, ocular irritancy, and accelerated stability testing. Results: Pre-formulation study confirmed the purity, solubility, and compatibility of drug measured by λmax, partition coefficient, stability study, and Fourier-transform infrared spectroscopy (FTIR) analysis. Taguchi screening method suggested about 12 different formulations and 3 most prominent influential factors including viscosity, GT, and drug release. 13 different formulations designed based on ‘BBD’ method were further optimised by considering the most influential factors suggested by Taguchi screening. The in vitro evaluation of the optimised formulation gave satisfactory results in terms of drug release, and anti-microbial activity. It was found to be isotonic with no ocular irritancy. Further, the preparation immediately transformed from sol to gel upon administration into cul-de-sac region of the eye due to multi-dimensional approaches utilised for in-situ gel formation namely temperature change Pluronic, ion sensitivity due to Gellan-gum, pH sensitivity because of Carbopol. Conclusion: The optimised in-situ gelling ocular drug formulation showed promising potency for ophthalmic drug delivery with no irritancy due to the multifactorial mechanism.

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