Formulation and optimization of duloxetine hydrochloride buccal films: <i>in vitro</i> and <i>in vivo</i> evaluation

Sharawy, Amr Mostafa El; Shukr, Marwa Hassan; Elshafeey, Ahmed Hassen

doi:10.1080/10717544.2017.1402216

Cited by 26 publications

(18 citation statements)

References 39 publications

(45 reference statements)

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“…Clinically prescribed oral duloxetine hydrochloride (30 mg, 60 mg and 120 mg once a day) has limited therapeutic efficacy in terms of intolerable side effects such as hepatic impairment, renal insufficiency, weight gain, anorexia, fatigue, dry mouth etc and poor nerve repair ( Cruccu, 2007 ; Dworkin et al, 2007 ). Moreover, oral administration demonstrates poor bioavailability (≈50 %) due to first pass metabolism ( Sharawy et al, 2017 ). Consequently, an alternative and more successful delivery may be a superior option that could ensures its safe use to manage CIPN symptoms.…”

Section: Introductionmentioning

confidence: 99%

Duloxetine hydrochloride loaded film forming dermal gel enriched with methylcobalamin and geranium oil attenuates paclitaxel-induced peripheral neuropathy in rats

2020

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Objective In attempt to conquer the major concerns of oral duloxetine hydrochloride (like low bioavailability, intolerable side-effects and no regeneration of demyelinated nerve fibres) for the management of chemotherapy-induced peripheral neuropathy (CIPN), an alternative delivery of duloxetine hydrochloride was aimed for in-vivo optimization. Methods A film forming dermal gel consisting of duloxetine hydrochloride was formulated and enriched with methylcobalamin and geranium oil. The formulated gel successfully qualified the various pharmaceutical characteristics of gel. Administration of paclitaxel (8 mg/kg/ i.p. in four divided doses) for 4 alternate days induced the symptoms of peripheral neuropathy in rats. On 14th day, the responses to noxious stimulus (mechanical hyperalgesia, cold allodynia, and heat hyperalgesia) were increased and reached to its maximum. Thereafter, drug treatment with formulated dermal gel and oral duloxetine hydrochloride (30 mg/kg, once daily) was initiated for 2 weeks in different group of animals. On the 28th day animals were sacrificed to isolate sciatic nerve, to assess biochemical changes (TBARS, reduced GSH, total protein, TNF-α, IL-6) and for histopathological examinations of nerve sections using Hematoxylin-Eosin and Toludine blue staining methods. Results Application of formulated dermal gel to paclitaxel-treated rats significantly improved paw-withdrawal latency responses during noxious stimulus testing, reduced the levels of TBARS, TNF-α, IL-6 and elevated the levels of reduced GSH as compared to paclitaxel treated rats. Histographs also indicated marked regeneration of the damaged nerve fibers. Topical delivery of duloxetine hydrochloride produced similar results in disparity to oral route. However, no significant disparity in responses was obtained with twice application of formulated dermal gel when compared to once daily application. Conclusion Tremendous recovery from nociception, oxidation and inflammation in addition to nerve degeneration was achieved through dermal application of duloxetine hydrochloride in peripheral neuropathy.

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Section: Introductionmentioning

confidence: 99%

Duloxetine hydrochloride loaded film forming dermal gel enriched with methylcobalamin and geranium oil attenuates paclitaxel-induced peripheral neuropathy in rats

2020

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“… 46 Swelling characters and the formation of strong hydrogen bonding with mucin are attributed to the mucoadhesion behavior of HPMC. 47 , 48 In addition, CRP is reported for its mucoadhesive character that augments the mucoadhesive properties of HPMC film. The repulsion forces between ionized carboxylate moiety, on CRP backbone (p K around 6.0), at pH of the buccal cavity (6.2-7.6) that leads to swelling of CRP.…”

Section: Resultsmentioning

confidence: 99%

Improved Transmucosal Delivery of Glimepiride via Unidirectional Release Buccal Film Loaded With Vitamin E TPGS-Based Nanocarrier

et al. 2020

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Glimepiride (GMD) is a hypoglycemic agent that has variation in bioavailability for its unexpected absorption. Glimepiride was formulated in a buccal film loaded with a nanobased formulation to enhance its absorption via buccal mucosa. Nanostructured lipid carriers (NLCs) and d-α-tocopherol polyethylene glycol 1000 succinate-based micelles enhance GMD solubility and improve its permeation through the buccal mucosa. The formulation variables were optimized using a Box-Behnken design. These factors, such as the percent of micelles relative to NLC ( X 1), the percent of Carbopol ( X 2), and the percent of permeation enhancer ( X 3), were investigated for their effect on the initial release ( Y 1) and the cumulative release after 6 hours ( Y 2). The optimum levels for X 1, X 2, and X 3 were 100%, 0.05%, and 1.8%, respectively. The optimized formulation revealed that the permeation of GMD from the film was in favor of micelles. This optimized film was then coated with ethyl cellulose to direct the release only through the buccal mucosa. The optimized unidirectional GMD transmucosal film showed a release of 93.9% of GMD content at 6 hours compared to 60.41% of GMD release from the raw GMD film. This finding confirmed the suitability of transmucosal delivery of GMD via the buccal mucosa.

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“…Formulation F2 followed controlled release phenomena for the drug release and fitting the in vitro data in to Peppas model indicated with proved n and R 2 values that the release of KTM was non-Fickian type of diffusion (Table 4) [33]. This results lead to an assumption that the drug followed both paracellular and transcellular pathways for its permeation [21].…”

Section: Mucoadhesion Strengthmentioning

confidence: 93%

Preparation of Carbopol 934 Based Ketorolac Tromethamine Buccal Mucoadhesive Film: In Vitro, Ex Vivo, and In Vivo Assessments

Begum

Alqahtani

Ghazwani

et al. 2021

International Journal of Polymer Science

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The goal of present investigation was to formulate and evaluate ketorolac tromethamine (KTM) mucoadhesive buccal films. The films were prepared by solvent evaporation method using PVP K30, HPMC K4M, HPMC K15M, carbopol 934, chitosan, and sodium alginate as polymers and propylene glycol as plasticizer. The films were evaluated for thickness, weight variation, folding endurance, surface pH, swelling index, in vitro residence time, in vitro diffusion, release kinetics, ex vivo permeation, in vitro-ex vivo correlation, and in vivo pharmacological activities such as anti-inflammatory and analgesic activity. Thickness, weight, drug content, and folding endurance were found to be uniform for the films. Surface pH was 6.85 ± 0.10 , and swelling index was the highest ( 27.27 ± 0.37 ) for the best film containing carbopol 934 along with sodium alginate and PVP K 30 (formulation code F2). In vitro residence time was greater than 5 h, and in vitro % drug release was 98.71% for F2. It exhibited 55.49% of swelling inhibition at 5 h, and above 38.88% was maintained at even 8 h. The film F2 has shown maximum analgesic response of 17 sec at 5 h, and the response of 11 sec was maintained at even 8 h. The anti-inflammatory and analgesic effect of F2 was found be maximum while sustaining the effect for prolonged period when compared to free drug solution. Thus, KTM mucoadhesive buccal film containing carbopol 934, sodium alginate, and PVP K30 could be an effective alternative for conventional therapy with improved efficacy.

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Formulation and optimization of duloxetine hydrochloride buccal films: in vitro and in vivo evaluation

Cited by 26 publications

References 39 publications

Duloxetine hydrochloride loaded film forming dermal gel enriched with methylcobalamin and geranium oil attenuates paclitaxel-induced peripheral neuropathy in rats

Duloxetine hydrochloride loaded film forming dermal gel enriched with methylcobalamin and geranium oil attenuates paclitaxel-induced peripheral neuropathy in rats

Improved Transmucosal Delivery of Glimepiride via Unidirectional Release Buccal Film Loaded With Vitamin E TPGS-Based Nanocarrier

Preparation of Carbopol 934 Based Ketorolac Tromethamine Buccal Mucoadhesive Film: In Vitro, Ex Vivo, and In Vivo Assessments

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