Abstract
Purpose: Biopharmaceutics classification system (BCS) class IV compounds, exhibits least oral bioavailability, low solubility and intestinal permeability among all pharmaceutical classes of drugs. Thus, these drugs need more compatible and efficient delivery system. Since, their solubility in various medium, remains a limitation so, polymeric nano coacervates based drug loading with modified approach for them may prove to be a solution ahead. Therefore, in present study Chitosan is opted for encapsulating the BCS class IV drug (Hydrochlorothiazide) to attain better stability, enhanced permeability and lower toxicity.Methods: For this study, Hydrochlorothiazide (HCTZ) was opted for formulating chitosan based nano-coacervate system.Results: Optimized HCTZ nanocoacervates exhibited the average particle size of 91.39 ± 0.75 nm with Poly-dispersity index score of 0.159 ± 0.01, indicating homogeneity of colloidal solution. Zeta potential and encapsulation efficiency of HCTZ nanocoacervates were recorded as -18.9 ± 0.8 mV and 76.69 ± 0.82 % respectively. Further, from TEM and SEM evaluation the average particle size for the same were found in conformity (35-50 nm), with almost spherical morphology. Also, the EDX (Electron Dispersive X-ray) spectrometry and FT – IR analysis of optimized formulation indicated the balanced chemical composition and interaction between the polymeric molecules. The HCTZ nano coacervates showed the linear diffusion profile through the dialysis membrane.Conclusion: We can conclude from the present study that the optimized HCTZ nano coacervates may prove to be a suitable potential option for effective delivery of BCS class IV drugs.
Highlights
Based on the Bio pharmaceutics Classification System, drugs are classified into four categories depending on their solubility and permeability properties like class I compounds are the ones having higher solubility and permeability; class II representing lower solubility but higher permeability; class III showing higher solubility but less permeability; and lastly class IV compounds with very less count of solubility and permeability index.[3]
It was been observed that drug entrapment incremented with increasing chitosan concentration and NaOH Molarity but decreased after certain range (Chitosan concentration 2mg/ml, NaOH - 2.5M), reflecting the possibility of increased resistance created by higher degree of NaOH molarity, preventing the chitosan from drug encapsulation
It has been observed that the maximum entrapment efficiency of 76.69% (11th run*) and minimum of 46.07% (4th run*) was recorded from the designed model system which was in accordance with the experimental data (Table 2)
Summary
The drug absorption rate in gastrointestinal (GI) tract is impacted by plenty of factors, like physicochemical nature, size and molecular weight of the compounds, metabolic, physiological functions, structure and surface of the gut cells etc.[1,2] Notwithstanding this complexity, the Bio pharmaceutics Classification System (BCS) developed by Amidon et al.[3] and Lipinski et al, prominently indicated that the synthetically derived drug leads, enormously fabricated by introduction of highthroughput screening (HTS) and combinatorial chemistry but, on the other side they were facing challenges from poorly water soluble drugs.[4,5] Based on the Bio pharmaceutics Classification System, drugs are classified into four categories depending on their solubility and permeability properties like class I compounds are the ones having higher solubility and permeability; class II representing lower solubility but higher permeability; class III showing higher solubility but less permeability; and lastly class IV compounds with very less count of solubility and permeability index.[3]. Several approaches for improving drug delivery, solubility and permeability are constantly designed and modified, for class II and IV compounds. The approaches such as complexation, micronization, crystal modification, increasing the drug dissolution rate, higher solubilization of the drugs etc., are more explored but these techniques do have restrictions to improve the assimilation and permeability of class IV drugs. A more viable and effective approach to improvise and redesign the drug formulation with respect to its carrier system,
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