In the present study we have selected one such BCS class IV drug, Hydrochlorothiazide (HCTZ) 7 which is a well categorized Thiazide diuretic, considered as the first-line of treatment for hypertension and listed as an essential medicine in WHO list. Therefore, a more viable and effective approach to improvise and redesign the drug formulation with respect to its carrier system, encapsulation and its targeted release is focused upon. In addition, very less count of therapeutic compounds, out of the millions, being tested each day, reaches the market. 5, 6 Nevertheless, discovering a novel therapeutic agent is a tough, time consuming and high cost bearing approach. Consequently, the best solution to improve the bioavailability of these drugs would be to return to the lead optimization phase of drug discovery and alter their structures to obtain the appropriate physicochemical properties. 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.
Now, several approaches for improving drug delivery, solubility and permeability are constantly designed and modified, specifically for class II and IV compounds. 3 Afterwards when this classification system was deeply dwelled and studied, it came in to the light that drug formulation and their carrier system areequally responsible in determining the rate and extent of absorption in GIT, increasing the bioavailability and therapeutic index of the classified 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 and Lipinski et al., prominently indicated that the synthetically derived drug leads, enormously fabricated by introduction of high-throughput screening (HTS) and combinatorial chemistry but, on the other side they were facing challenges from poorly water soluble drugs. 1, 2 Notwithstanding this complexity, the Bio pharmaceutics Classification System (BCS) developed by Amidon et al. 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. The HCTZ nano coacervates showed the linear diffusion profile through the dialysis membrane.Ĭonclusion: 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. 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. Further, from TEM and SEM evaluation the average particle size for the same were found in conformity (35-50 nm), with almost spherical morphology. Zeta potential and encapsulation efficiency of HCTZ nanocoacervates were recorded as -18.9 ± 0.8 mV and 76.69 ± 0.82 % respectively. 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.
Methods: For this study, Hydrochlorothiazide (HCTZ) was opted for formulating chitosan based nano-coacervate system. Therefore, in present study Chitosan is opted for encapsulating the BCS class IV drug (Hydrochlorothiazide) to attain better stability, enhanced permeability and lower toxicity. 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. Thus, these drugs need more compatible and efficient delivery system. Purpose: Biopharmaceutics classification system (BCS) class IV compounds, exhibits least oral bioavailability, low solubility and intestinal permeability among all pharmaceutical classes of drugs.