Alternativas farmacéuticas: ¿pueden ser intercambiables?

2020 ◽  
Vol 2 (2) ◽  
pp. 38-42
Author(s):  
Miriam del Carmen Carrasco-Portugal ◽  
Francisco Javier Flores-Murrieta
Keyword(s):  
Generic Substitution ◽  
In Vivo Studies ◽  
Regulatory Agencies ◽  
European Medicines Agency ◽  
Reference Formulation ◽  
Active Moiety ◽  
Significant Difference ◽  
Pharmaceutical Form ◽  
Extent Of Absorption

Pharmaceutical alternatives are products with the same active moiety, but different salt, ester or pharmaceutical form. Regulatory agencies have different criteria for this kind of drug. The European Medicines Agency (EMA) accepts the generic substitution using these alternatives, whereas the Food and Drug Administration (FDA) only authorizes generic substitution of pharmaceutical equivalents. The objective of this paper is to describe some relevant aspects that should be considered before deciding on making a generic substitution with pharmaceutical alternatives. It is important to note that a pharmaceutical alternative must show no significant difference in the rate and extent of absorption (bioequivalence) in a well-conducted in vivo study when compared with the reference formulation. Current Mexican regulations state that generic substitution is possible using pharmaceutical alternatives when bioequivalence is demonstrated in in vivo studies conducted under the NOM-177-SSA1-2013 criteria. In conclusion, generic substitution with pharmaceutical alternatives is possible if these products demonstrate in vivo bioequivalence when compared with the reference product.

scholarly journals International Regulations for Bioequivalence Approval of Locally Acting Orally Inhaled Drug Products

2021 ◽  
Author(s):  
Dr. Vinod Gaikwad ◽  
Prajakta Patil ◽  
Atmaram Pawar ◽  
Kakasaheb Mahadik
Keyword(s):  
In Vivo Studies ◽  
Regulatory Agencies ◽  
European Medicines Agency ◽  
Drug Products ◽  
International Regulations ◽  
Orally Inhaled Drug Products ◽  
Drug Regulatory Agencies ◽  
Health Canada

Bioequivalence (BE) is established between the brand drug and the generic drug to allow the linking of preclinical and clinical testing conducted on the reference listed drug. Regulatory agencies around the globe have come up with the guidance for locally acting orally inhaled drug products (OIDPs) for bioequivalence approaches. The prime intent of the present article is to compare approaches of different international regulatory authorities such as Health Canada, European Medicines Agency and the US Food and Drug Administration that have published guidance related to locally acting OIDPs. Moreover, the Central Drugs Standard Control Organisation, India, has published guidelines for bioavailability and bioequivalence studies. BE recommendations from global regulatory agencies were based on comparison for different parameters, namely inhaler device, formulation, reference product’s selection, in-vitro as well as in-vivo studies (pharmacokinetics, pharmacodynamics, and clinical studies). In the case of in-vivo studies, details about study design, dose choices, inclusion/ exclusion criteria of the subject, study period, endpoint study, and equivalence acceptance criteria were discussed in the present review article.

scholarly journals Optimizing Manufacturing and Osseointegration of Ti6Al4V Implants through Precision Casting and Calcium and Phosphorus Ion Implantation? In Vivo Results of a Large-Scale Animal Trial

Materials ◽  
2020 ◽  
Vol 13 (7) ◽  
pp. 1670 ◽  
Author(s):  
Wölfle-Roos JV ◽  
Katmer Amet B ◽  
Fiedler J ◽  
Michels H ◽  
Kappelt G ◽  
...  
Keyword(s):  
Ion Implantation ◽  
Large Scale ◽  
In Vivo Studies ◽  
Control Group ◽  
Implant Surface ◽  
Precision Casting ◽  
Pull Out ◽  
Significant Difference ◽  
Calcium And Phosphorus

Background: Uncemented implants are still associated with several major challenges, especially with regard to their manufacturing and their osseointegration. In this study, a novel manufacturing technique—an optimized form of precision casting—and a novel surface modification to promote osseointegration—calcium and phosphorus ion implantation into the implant surface—were tested in vivo. Methods: Cylindrical Ti6Al4V implants were inserted bilaterally into the tibia of 110 rats. We compared two generations of cast Ti6Al4V implants (CAST 1st GEN, n = 22, and CAST 2nd GEN, n = 22) as well as cast 2nd GEN Ti6Al4V implants with calcium (CAST + CA, n = 22) and phosphorus (CAST + P, n = 22) ion implantation to standard machined Ti6Al4V implants (control, n = 22). After 4 and 12 weeks, maximal pull-out force and bone-to-implant contact rate (BIC) were measured and compared between all five groups. Results: There was no significant difference between all five groups after 4 weeks or 12 weeks with regard to pull-out force (p > 0.05, Kruskal Wallis test). Histomorphometric analysis showed no significant difference of BIC after 4 weeks (p > 0.05, Kruskal–Wallis test), whereas there was a trend towards a higher BIC in the CAST + P group (54.8% ± 15.2%), especially compared to the control group (38.6% ± 12.8%) after 12 weeks (p = 0.053, Kruskal–Wallis test). Conclusion: In this study, we found no indication of inferiority of Ti6Al4V implants cast with the optimized centrifugal precision casting technique of the second generation compared to standard Ti6Al4V implants. As the employed manufacturing process holds considerable economic potential, mainly due to a significantly decreased material demand per implant by casting near net-shape instead of milling away most of the starting ingot, its application in manufacturing uncemented implants seems promising. However, no significant advantages of calcium or phosphorus ion implantation could be observed in this study. Due to the promising results of ion implantation in previous in vitro and in vivo studies, further in vivo studies with different ion implantation conditions should be considered.

Use of Medium Potency Statins Is Associated with Improved Outcomes after Frontline RCHOP in Patients with Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 45-45
Author(s):  
Sushanth Gouni ◽  
Paolo Strati ◽  
Jason Westin ◽  
Loretta J. Nastoupil ◽  
Raphael E Steiner ◽  
...  
Keyword(s):  
Cell Lines ◽  
Research Funding ◽  
Response Assessment ◽  
Cholesterol Content ◽  
In Vivo Studies ◽  
High Cholesterol ◽  
Improved Outcomes ◽  
Significant Difference

Background: Pre-clinical studies show that statins may improve the efficacy of chemoimmunotherapy in patients with DLBCL, through interference with cell membrane-initiated signaling pathways. Clinical retrospective studies, however, yield conflicting data, due to heterogeneous properties of statins, including potency and hydrophilicity. Methods: This is a retrospective analysis of patients with previously untreated, advanced stage DLBCL, non-double hit, treated with frontline R-CHOP between 01/01/2000 and 09/01/2019 (data cut-off 04/15/2020) at MD Anderson Cancer Center, and for whom data regarding statin use at time of initiation of treatment were available. Lugano 2014 response criteria were applied retrospectively for response assessment. Cellular cholesterol levels were analyzed in 6 DLBCL cell lines using an Amplex red fluorometric assay. A doxorubicin (DXR)-resistant cell line was generated exposing SUDHL4 cells to escalating doses of DXR; a DXR-resistant DLBCL patient-derived xenograft (PDX) model was established through serial transplantation and exposure to DXR. Results: 271 patients were included in the analysis, 182 (67%) were older than 60 years, 134 (49%) were male, 212 (72%) had stage IV disease, and 217 (80%) had an IPI score > 3; upon pathological review, 38 (36%) cases were non-GCB type, and 18 (28%) were double-expressors; 214 (79%) were able to complete all planned 6 cycles of RCHOP. Seventy-nine (29%) patients received statins at time of initiation of chemoimmunotherapy: 15 patients received low potency statin, 51 medium and 13 high; 18 patients received hydrophilic statins and 61 lipophilic. Patients receiving statins were significantly older as compared to patients who did not (p<0.001); no other significant difference in baseline characteristics was observed when comparing the 2 groups. Overall, 265 out of 271 patients were evaluable for response, as 6 stopped treatment because of toxicity before first response assessment. Among these, ORR was 95% (252/265) and CR rate was 62% (165/265). ORR rate was identical in patients who were treated with statin and those who did not (95% both, p=1). After a median follow-up of 77 months (95% CI, 70-84 months), 119 patients progressed/died, median PFS was not reached and 6-year PFS was 57%. 6-year PFS rate according to statin intensity was: 48% (low), 72% (medium), 57% (high). PFS. 6-year PFS rate was 64% for hydrophilic and 72% for lipophilic statins. Patients treated with statins had a trend for longer PFS (p=0.06), significantly longer for patients receiving medium potency statins (p=0.04). No significant difference in PFS was observed when comparing patients treated with lipophilic statins to all others (not reached vs 84 months, p=0.22). To confirm these clinical data, in-vitro and in-vivo studies were performed. Six cell lines were tested: 4 with high cholesterol content (SUDHL4, HBL1, HT, and U2932; 5.0-8.0 µg/mg protein), and 2 with low cholesterol content (DOHH2 and OCI-LY19; 1.5-2.0 µg/mg protein); the latter showed the highest sensitivity to DXR-mediated killing. The combination of lovastatin and DXR (10nM) was tested in all 4 cell lines with high cholesterol content, resulting in more cell death than either treatment alone. Lovastatin (at the nanomolar range) resensitized DXR-resistant SUDHL4 cells to DXR. Finally, in a DXR-resistant PDX model, the combination of lovastatin and DXR resulted in delayed tumor growth as compared to chemotherapy alone. Conclusions: Use of medium potency statins is associated with improved outcomes after frontline RCHOP in patients with DLBCL. This was further confirmed in functional in-vitro and in-vivo studies. Future interventional studies, aimed at improving outcomes in these patients using this novel combination, are warranted. Disclosures Westin: Amgen: Consultancy; 47: Research Funding; Kite: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Curis: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding. Nastoupil:Gamida Cell: Honoraria; Merck: Research Funding; TG Therapeutics: Honoraria, Research Funding; Karus Therapeutics: Research Funding; Janssen: Honoraria, Research Funding; LAM Therapeutics: Research Funding; Novartis: Honoraria, Research Funding; Bayer: Honoraria; Celgene: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Gilead/KITE: Honoraria. Neelapu:Bristol-Myers Squibb: Other: personal fees, Research Funding; Merck: Other: personal fees, Research Funding; Kite, a Gilead Company: Other: personal fees, Research Funding; Pfizer: Other: personal fees; Celgene: Other: personal fees, Research Funding; Novartis: Other: personal fees; Karus Therapeutics: Research Funding; N/A: Other; Takeda Pharmaceuticals: Patents & Royalties; Acerta: Research Funding; Cellectis: Research Funding; Poseida: Research Funding; Precision Biosciences: Other: personal fees, Research Funding; Legend Biotech: Other; Adicet Bio: Other; Allogene Therapeutics: Other: personal fees, Research Funding; Cell Medica/Kuur: Other: personal fees; Calibr: Other; Incyte: Other: personal fees; Unum Therapeutics: Other, Research Funding. Landgraf:NCI/NIH: Research Funding. Vega:NCI: Research Funding.

scholarly journals Preparation and preclinical evaluation of aceclofenac loaded pectinate mucoadhesive microspheres

2012 ◽  
Vol 2 (1) ◽  
pp. 8 ◽  
Author(s):  
Santanu Chakraborty ◽  
Priyanka Nayak ◽  
Bala Murali Krishna ◽  
Madhusmruti Khandai ◽  
Ashoke Kumar Ghosh
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Polymer Concentration ◽  
Research Work ◽  
In Vivo Studies ◽  
Systemic Absorption ◽  
Cross Linking ◽  
Significant Difference

The aim of the present research work was to fabricate aceclofenac loaded pectinate microspheres by ionic gelation method and evaluate the effect of different cross-linking agents and polymer concentration on particle size, encapsulation efficacy and drug release behavior. It was also investigated that whether this pectinate dosage form was able to target the drug release in intestinal region and prevent the different side effect associated with the drug in stomach or not. It was observed that particle size, encapsulation efficacy and in vitro drug release were largely depended on polymer concentration and cross-linking agents. It was also observed that pectinate microspheres showed excellent pH depended mucoadhesive properties and they were able to restrict the drug release in stomach. <em>In vitro</em> drug release study showed that alminium-pectinate microspheres have more sustaining property as compared to barium-pectinate microspheres. Holm-Sidak multiple comparison analysis suggested a significant difference in measured t<sub>50%</sub> values among all the formulations with same cross-linking agent. In vivo studies revealed that the anti inflammatory and analgesic effects induced by pectinate microspheres were significantly high and prolonged as compared to pure drug. So, pectinate microspheres can be an excellent carrier for targeting the delivery of aceclofenac as well as help in improving the patient compliance by prolonging the systemic absorption.

Effect of Single Dose In Vivo Propranolol Therapy on In Vitro Adhesion of Human SS RBC.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1234-1234 ◽  
Author(s):  
Laura M. De Castro ◽  
Jude C. Jonassaint ◽  
Jennifer G. Johnson ◽  
Milena Batchvarova ◽  
Marilyn J. Telen
Keyword(s):  
Safety Data ◽  
Study Drug ◽  
Flow Chamber ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Number Of Patients ◽  
Significant Difference ◽  
Before And After

Abstract Sickle red blood cells (SS RBC) are abnormally adhesive to both endothelial cells (ECs) and components of the extracellular matrix (ECM). Epinephrine (epi) has been shown to elevate cAMP in SS RBC and increase adhesion of SS RBC to ECs in a protein kinase A-dependent manner. In vitro and in vivo studies performed in our lab have led to the hypothesis that adrenergic stimuli such as epi may initiate or exacerbate vaso-occlusion and thus contribute to the association of vaso-occlusive events with physiologic stress. We are conducting a prospective, dose-escalation pilot clinical study to investigate whether in vivo administration of one dose of propranolol either down-regulates baseline SS RBC adhesion in vitro or prevents its upregulation by epi. In addition, this study will provide additional safety data regarding the use of propranolol in normotensive patients with sickle cell disease (SCD). Figure Figure To date, we have completed the first two dose cohorts. 11 subjects (9 SS and 1 Sβ° thalassemia; 7 females, 3 males) have participated. No severe adverse events were noted. Cohorts 1 and 2 had mean pre-propranolol blood pressure (BP) of 116 (5.9 SD)/ 60.4 (3.98 SD) and 106.8 (4.68 SD)/ 58 (3.9 SD), respectively; this difference was not statistically significant. Minimal and asymptomatic changes in BP were noted in both cohorts after drug administration, with biphasic systolic and diastolic BP nadirs at 45 and 240 minutes. No clinically significant changes in heart rate were observed. Adhesion studies were performed using a graduated height flow chamber on the day of RBC collection. RBC adhesion to ECs was studied before and after epi stimulation and was measured at sheer stresses ranging from 1 to 3 dyne/cm2. Baseline adhesion measurements were validated by comparing percent (%) adhesion assayed at 2 different times within 7 days—at screening and before propranolol dose on the study drug day. We observed no significant difference in adhesion at the 2 different time points without propranolol. Comparison of % adhesion of epi-stimulated RBC to ECs before and 1 hour after propranolol showed that propranolol given in vivo significantly inhibited both non-stimulated and epi-stimulated SS RBC adhesion (p=0.04 and p=0.001, respectively). Lastly, comparison of SS RBC adhesion at both drug doses confirmed the drug-related inhibition of adhesion (p&lt;0.004). We conclude that propranolol administered in vivo decreases SS RBC baseline adhesion to ECs and substantially abrogates epi-stimulated adhesion to ECs, as measured in vitro. Although we have thus far studied only a small number of patients and low propranolol doses, we expect to confirm these results with the 3rd cohort, in which a higher dose of propranolol will be used. If our findings continue to show that propranolol can decrease both SS RBC baseline and epi-stimulated adhesion to ECs, study of propranolol on a larger scale would be warranted in order to ascertain its safety and efficacy as an anti-adhesive therapy in SCD.

scholarly journals Bioanalysis and in-vivo studies of clarithromycin modified release solid dosage formulations by liquid chromatography-mass spectroscopy

2020 ◽  
Vol 11 (1) ◽  
pp. 87-92
Author(s):  
Nagarajan Janaki Sankarachari Krishnan ◽  
Elango Kannan
Keyword(s):  
Biological Fluid ◽  
Internal Standard ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Modified Release ◽  
Reference Formulation ◽  
Release Formulation ◽  
Solid Dosage ◽  
Test Formulation

The current study was undertaken to develop the new bioanalytical method and validation for determining Clarithromycin by LC-MS Method and as well as to conduct in vivo studies. Princeton octadecyl silane column (10 cm x 4.6 mm id, 5µm) used as adsorbent and cyanomethane: 0.5 % Methanoic acid was treated as the eluent for the separation of the analyte from the biological fluid in an isocratic mode having the ratio 60:40 % v/v and 0.5 ml/min as flow rate, and injection volume was set as 20 µl. APCI and the mass detected of Clarithromycin and Azithromycin (act as internal standard) was detected at 748.45 and 749.70, respectively. Developed bioanalytical methods have been used to quantify the Pharmacokinetic parameters like Cmax, Tmax, AUC0-t & AUC0-∞, Keli, and t1/2 studied and the values for reference formulation (3.382µg/ml, 7.333 h, 114.429µg.h/ml, 131.435µg.h/ml, 0.031 h-1, and 23.397h respectively) and the test formulation (3.847 µg/ml, 7.417 h, 132.318 µg.h/ml, 151.388 µg.h/ml, 0.031 h-1, and 23.187 h, respectively) were compared and found to be bioequivalent. Based on our study, the test formulation of Clarithromycin modified-release formulation containing 500 mg of Clarithromycin is Bioequivalent to that of the reference.  Compare to our method (LC-MS) is simple, sensitive, precise as well as comparable with the reference formulation of the modified release product of clarithromycin 500 mg.

scholarly journals Formulation and Evaluation of Fast Dissolving Film of Losartan Potassium

2021 ◽  
Vol 68 (1) ◽  
Author(s):  
Bhageerathy A ◽  
Sandhya Murali ◽  
eny Sara Thomas ◽  
Sigi Vasanthkumar ◽  
Prasanth V V
Keyword(s):  
Drug Release ◽  
Physical Stability ◽  
Losartan Potassium ◽  
In Vivo Studies ◽  
Disintegration Time ◽  
Drug Content ◽  
Weight Variation ◽  
Significant Difference

A total of nine formulations of fast dissolving films of Losartan Potassium were developed by solvent casting method using film forming polymers such as HPMC E5, E15 and E50 and other film modifiers. The appearances of films were transparent, thin, flexible, elastic, smooth and transparent. The weight variation ranged between 16.14 ± 0.192 and 17.31 ± 0.313 and showed that there was no significant difference in the weight of individual formulations. All the formulations showed more than 150 of folding endurance. The drug content was found to be in an acceptable range for all the formulations which indicated uniform distribution of drug. A rapid dissolution of all the film was observed by the dissolution test, in which above 90% of Losartan Potassium was released within 5 min. The formulation F1 showed maximum drug release (98.73) within 5 minutes. Based on the in vitro drug release, drug content and in vitro disintegration time it is found that F1 was selected as the best formulation. The formulations showed satisfactory physical stability at 40°C at 75 % RH. Losartan Potassium (LOSAR-25) is shown in Figure 4. From the results of comparative studies of marketed product and it found that F1 showed 98.73% release within 5 min and LOSAR 25 showed 90.76% release in 30 min. In vitro studies indicate that this potential drug delivery system has considerably good stability and release profile. Nevertheless, further in vivo studies are warranted to confirm these results.

scholarly journals Effects of photopolymerisation on genotoxicity of composite adhesives in the comet assay

Genetika ◽  
2016 ◽  
Vol 48 (2) ◽  
pp. 617-627
Author(s):  
Stefan Dacic ◽  
Ninoslav Djelic ◽  
Milena Radakovic ◽  
Nada Lakic ◽  
Aleksandar Veselinovic ◽  
...  
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Human Lymphocytes ◽  
Negative Control ◽  
In Vivo Studies ◽  
Halogen Lamp ◽  
Genotoxic Effects ◽  
Significant Difference ◽  
Isolated Human Lymphocytes

Certain in vivo studies have shown that the application of adhesives directly onto the open pulp or on a thin layer of dentin causes inflammation and pulpal abscesses. This reaction is related to toxic effects of monomers from adhesives. It has been confirmed that after proper illumination the adhesives become less toxic. The aim of the study was to examine genotoxicity of non-polymerised, partly polymerised and polymerised adhesives on isolated human lymphocytes using the alkaline Comet assay. Adper Single bond2 and Adper Easy One/3M ESPE adhesive photopolymerisation was performed by Elipar Highlight 3M ESPE halogen lamp for 0, 10 and 40 sec, at final concentrations of 100, 200, 500 and 1000 ?g/mL. With both adhesives, photopolymerisation at 0 and 10 seconds showed statistically significant increase in DNA damage in comparision to the negative control (solvent). On the other hand, after 40 seconds of photopolymerisation of both adhesives in all tested concentrations, the degree of DNA damage in Comet assay had no significant difference (P>0.05, ?2 test) compared to the negative control. Therefore, only the 40 seconds of photopolymerisation prevented genotoxic effects of both adhesives in the Comet assay.

Steroid effects on permeability of rat thymic lymphocytes to α-aminoisobutyrate

1963 ◽  
Vol 205 (3) ◽  
pp. 446-452 ◽  
Author(s):  
Melvin Blecher
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Fluid ◽  
In Vivo Studies ◽  
Metabolic Inhibitors ◽  
Active Process ◽  
Low Concentrations ◽  
Significant Difference ◽  
Adrenalectomized Rats

In vitro studies of the flux of α-aminoisobutyrate-1-C14 (AIB) between rat thymic lymphocytes and extracellular fluid have revealed that: a) the amino acid enters cells but is not further metabolized; b) at low concentrations, similar to those of amino acids in plasma, the net influx and efflux of AIB exhibit properties of an active process; and c) influx of AIB is inhibited, and efflux stimulated, by deoxycorticosterone (DOC), by metabolic inhibitors, and by other specific steroids. In vivo studies of the distribution of AIB between serum and tissue demonstrated that administration of DOC to adrenalectomized rats inhibited concentration of AIB by thymus, diaphragm, and skeletal muscle, augmented uptake by liver, and increased the serum level of AIB. Prior adrenalectomy of donor rats resulted in no change from normal in the in vitro capacity of thymic lymphocytes to take up AIB. There was no significant difference from normal in the in vivo concentration of AIB by thymus, liver, and skeletal muscle of adrenalectomized rats, although uptake by diaphragm was decreased compared to normal control animals.

Pharmacokinetic Profile of Oxaliplatin-Loaded pH-Responsive Hydrogels in Rabbits

2020 ◽  
Vol 26 (44) ◽  
pp. 5755-5763
Author(s):  
Kaleem Ullah ◽  
Shujaat Ali Khan ◽  
Muhammad Sohail ◽  
Abdul Mannan ◽  
Ghulam Murtaza
Keyword(s):  
Drug Release ◽  
Drug Loading ◽  
Oral Solution ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Platinum Compound ◽  
In Vivo Evaluation ◽  
Significant Difference

Background: Oxaliplatin (OXP), a 3rd generation platinum compound, which causes severe side effects due to; impulse high concentration in the bloodstream thereby exposing healthy cells at a high ratio, nonspecific delivery at the target site and non-compliance is administered intravenously. Objective: The project was aimed at the development, characterization, and in-vitro and in-vivo evaluation of pHresponsive hydrogels for oral administration of OXP. Methods: Hydrogel formulations were synthesized through a free radical polymerization technique followed by brief characterization using various techniques. The hydrogels were investigated for various in-vitro studies such as sol-gel, drug loading, swelling, drug release, and MTT-assay. While in-vivo studies such as oral tolerability, histopathology, and hematology studies were performed on rabbits. A simple and sensitive HPLC-UV method was optimized and the comparative pharmacokinetic study was performed in rabbits using OXP-oral solution and OXP-loaded hydrogels. Results: In-vitro characterization confirmed that the reactant was successfully crosslinked to form thermally stable hydrogels with decreased crystallinity and rough surface. Swelling and drug release showed that hydrogels were more responsive to basic pH (6.8 and 7.4) in comparison with pH 1.2. The blank hydrogels were cytocompatible as more than 95% of the cells were viable while free OXP and OXP-loaded hydrogels displayed dosedependent cytotoxic effect. In-vivo studies confirmed that chitosan and gelatin hydrogel suspension was well tolerable up to 3800 mg/kg and 4000 mg/kg of body weight, respectively. Hematology and serum chemistry reports were well within the range suggesting normal liver and kidney functions. Similarly, histopathology slides of rabbit vital organs were also found normal without causing any histopathological change. Conclusion: HPLC-UV method was successfully optimized for OXP detection in oral solution and hydrogels administered to rabbits. A significant difference was found among various pharmacokinetic parameters by comparing the two groups including half-life (t1/2), tmax, Cmax, AUCtot MRT, Vz, and Lz.

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