Formulation Development for Preclinical in vivo Studies

Suitable ex vivo models are required as predictive tools of oromucosal permeability between in vitro characterizations and in vivo studies in order to support the development of novel intraoral formulations. To counter a lack of clinical relevance and observed method heterogenicity, a standardized, controlled and physiologically relevant ex vivo permeation model was established. This model combined the Kerski diffusion cell, process automation, novel assays for tissue integrity and viability, and sensitive LC-MS/MS analysis. The study aimed to assess the effectiveness of the permeation model in the sublingual formulation development of cyclobenzaprine, a promising agent for the treatment of psychological disorders. A 4.68-fold enhancement was achieved through permeation model-led focused formulation development. Here, findings from the preformulation with regard to pH and microenvironment-modulating excipients proved supportive. Moreover, monitoring of drug metabolism during transmucosal permeation was incorporated into the model. In addition, it was feasible to assess the impact of dosage form alterations under stress conditions, with the detection of a 33.85% lower permeation due to salt disproportionation. Integrating the coherent processes of disintegration, dissolution, permeation, and metabolization within a physiological study design, the model enabled successful formulation development for cyclobenzaprine sublingual tablets and targeted development of patient-oriented drugs for the oral cavity.

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Formulation Development and Characterization of Rilpivirine Nanosuspension for Improved Solubility by Nanomilling

Asian Journal of Organic & Medicinal Chemistry ◽

10.14233/ajomc.2019.ajomc-p210 ◽

2019 ◽

Vol 4 (2) ◽

pp. 130-137

Author(s):

Satya Sankar Sahoo ◽

Chandu Babu Rao

Keyword(s):

Zirconium Oxide ◽

Particle Diameter ◽

In Vivo Studies ◽

X Ray Diffraction ◽

Formulation Development ◽

Flow Properties ◽

X Ray ◽

Sedimentation Volume

The objective of this study was to formulate and optimize a stable rilpivirine nanosuspension. In the present study, yttrium stabilized zirconium oxide beads being used as the milling media in nanomilling process. The lyophilized nanocrystals were being characterized by particle size distribution (PSD), polydispersity index (PDI), X-ray diffraction (XRD) and FTIR (Fourier transform infrared spectroscopy). Optimized nanosuspension has mean particle diameter of 266 nm, PDI of 0.158, zeta potential of 22.1 mV and spherical in shape with surface oriented stabilizer molecules. Flow properties like sedimentation volume, poura-bility with the F value of 0.94 and also the redispersability even after 4 weeks of storage was found to be satisfactory for the optimized nano-suspension. Many folds increase in solubility and rate of drug release observed, The lyophilized nanocrystals retains its crystallinity after nanomilling, stable chemically with high drug content, therefore, the developed nanosuspension would be an alternative better formulation than its conventional formulation to address its bioavailability issue. However, this should be further confirmed by appropriate techniques in vivo studies.

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ORAL DELIVERY OF ZOLMITRIPTAN LOADED FAST DISINTEGRATING FILM: FORMULATION DEVELOPMENT, STATISTICAL OPTIMIZATION, IN-VITRO AND IN-VIVO EVALUATION

Journal of Applied Pharmaceutical Sciences and Research ◽

10.31069/japsr.v2i1.3 ◽

2019 ◽

pp. 13-22 ◽

Cited By ~ 1

Author(s):

Iti Chauhan ◽

Mohammad Yasir ◽

Madhu Verma

Keyword(s):

Oral Delivery ◽

Stability Study ◽

In Vivo Studies ◽

Pharmacokinetic Parameters ◽

Albino Rats ◽

Formulation Development ◽

In Vivo Evaluation ◽

Disintegration Time

Introduction: Fast dissolving film technology has been developed out as a alternative drug delivery system that gives an exception advantage for taking medications. Objective: The aim of this study was to formulate and evaluate the Zolmitriptan loaded fast disintegrating oral film by solvent casting method. Material and methods: A preliminary study was conducted to select a suitable film forming polymer and plasticiser concentration.The formulation was optimized with the help of 22 factorial designs in which polymer and plasticizer concentration at two levels was taken as independent factors and disintegration time, tensile strength and % elongation were taken as dependent factors. The optimized formulation OP1 was subjected to stability study as per the ICH guidelines at 40 ± 0.50C / 75 ± 5% RH for six months. In vivo studies were conducted on Wister albino rats and concentration of drug in blood was analysed by HPLC technique. Various pharmacokinetic parameters for OP1 were determined and compared with reference formulation (drug sol.). Result and Discussion: For optimized formulation various parameters were found to be in acceptable range and it was stable under specified conditions. The value of AUC0–t (ng h/ml), AUC0–∞ (ng h/ml) of the OP1 was found to be 723.91± 84.21, 770.90 ± 104.32, respectively, for the drug sol 468.56 ± 79.36, 500.37 ± 95.43 respectively. Relative bioavailability of OP1 was 1.55 time than that of drug sol. Conclusion: The formulation not only increases the bioavailability of drug but also produce the quick action for the migraine patients.

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FORMULATION DEVELOPMENT OF ORLISTAT NANOCRYSTALS: IN VITRO CHARACTERIZATION AND IN VIVO STUDIES

INDIAN DRUGS ◽

10.53879/id.58.11.11880 ◽

2021 ◽

Vol 58 (11) ◽

pp. 29-37

Author(s):

Momin Munira ◽

◽

Apurva Kadam ◽

Chintan Bhavsar ◽

Anisha D’Souza

Keyword(s):

Treatment Time ◽

In Vivo Studies ◽

High Density Lipoproteins ◽

Control Group ◽

Sprague Dawley ◽

Formulation Development ◽

Subsequent Increase ◽

Sd Rats

Poor solubility of orlistat limits its luminal concentration and hence needs to be administered in higher doses, leading to drug related side effects. The aim of the present research was to investigate nanocrystallization approach to increase the solubility of orlistat using melt extrusion and high-pressure homogenization (HPH) methods. The effect of factors like type and amount of polymer, homogenization pressure and time, and number of cycles on orlistat solubility was investigated. A ~10-fold increase in the solubility of orlistat was attained using OPo11N with a subsequent increase in the dissolution rate of the drug. Poloxamer 188-orlistat nanocrystals (OPo11N) as compared to pure orlistat led to a decrease in T90%(20 mins for OPo11N and 51 mins for marketed sample). In vivo studies in female Sprague Dawley (SD) rats showed that post one month of oral administration the total cholesterol and low-density lipoproteins of female SD rats remained unchanged compared to the control group. The triglycerides content and high-density lipoproteins levels were significantly increased with increase in the treatment time i.e. 12 weeks compared to the group treated with pure orlistat drug. In conclusion, the NC approach could serve as an effective formulation strategy for solubility enhancement of orlistat.

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Improved Analgesic and Anti-Inflammatory Effect of Diclofenac Sodium by Topical Nanoemulgel: Formulation Development—In Vitro and In Vivo Studies

Journal of Chemistry ◽

10.1155/2020/4071818 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Shadab Md ◽

Nabil A. Alhakamy ◽

Hibah M. Aldawsari ◽

Sabna Kotta ◽

Javed Ahmad ◽

...

Keyword(s):

Diclofenac Sodium ◽

In Vivo Studies ◽

Gelling Agent ◽

Paw Edema ◽

Formulation Development ◽

Anti Inflammatory ◽

Development In Vitro ◽

Inflammatory Effect

The present study aimed to develop diclofenac sodium nanoemulgel for managing pain and inflammation using the low-energy emulsification technique. Nanoemulsion of diclofenac was formulated using clove oil with adequate amount of surfactants and cosurfactants, and it was converted to hydrogel form using Carbopol 980 as the gelling agent. The droplet size of the oil globules in the nanoemulsion was found to be 64.07 ± 2.65 nm with a low polydispersity index (0.238 ± 0.02) along with high negative zeta potential (−39.06 mV). The developed nanoemulgel exhibited non-Newtonian and pseudoplastic behavior. The in vitro release profile of the developed nanoemulgel was higher as compared to marketed and conventional gel. The carrageenan-induced paw edema test was performed in rats to evaluate the anti-inflammatory activity of developed nanoemulgel. The developed nanoemulgel showed significantly higher (p<0.01) effect in reducing pain and inflammation symptoms as compared to marketed as well as conventional gel of diclofenac. The overall findings of the study suggest that the developed nanoemulgel formulation of diclofenac can be used as a potential approach for the management of pain and inflammation.

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Formulation Development and in vivo Evaluation of Nevirapine Solid Dispersions by Solvent Evaporation Technique

International Journal of Pharmaceutical Sciences and Drug Research ◽

10.25004/ijpsdr.2018.100304 ◽

2018 ◽

Vol 10 (03) ◽

Author(s):

D.V.R.N Bhikshapathi ◽

Medipalli Viswaja,

Keyword(s):

Solid Dispersion ◽

Solid Dispersions ◽

Solvent Evaporation ◽

Water Soluble ◽

In Vivo Studies ◽

In Vitro Dissolution ◽

Formulation Development ◽

Amorphous Form ◽

Evaporation Technique

The objective of the present investigation is focused on the preparation of solid dispersions containing Nevirapine. The effect of various hydrophilic polymers on the aqueous solubility was studied. Kolliphor P188 was selected as carrier and solid dispersions were prepared by solvent evaporation technique. Evaluation of solid dispersion for percentage yield, drug content and solubility were most appropriate. Solid dispersions of drug: Kolliphor P188 and SLS (1:3:1 ratio) (SE9) shown higher dissolution rate i.e. 98.6% compared with and pure drug (37.5%) and other formulations. Powder X-ray diffraction performed on solid dispersion showed that Nevirapine existed in the amorphous form within the solid dispersion formulation fabricated using the solvent evaporation process. Additionally, scanning electron microscopy studies suggested the conversion of crystalline Nevirapine to an amorphous form. Therefore, the solid dispersions prepared by solvent evaporation method using Kolliphor P188 as hydrophilic carrier can be successfully used for improvement of solubility and dissolution of Nevirapine. Both in vitro dissolution testing and the in vivo studies demonstrated that the solubility and bioavailability of Nevirapine were significantly improved when formulated in a solid dispersion with Kolliphor P188 and SLS. The present study demonstrated that formulation of Nevirapine solid dispersion by solvent evaporation technique is a highly effective strategy for enhancing the bioavailability of poorly water soluble Nevirapine.

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