Design and development of colon targeted drug delivery system for colonic diseases

INTRODUCTION : Drug delivery system can be defined as the mechanisms to set up therapeutic agents into the body. Primitive approaches of delivering drugs lacked a very basic need in drug delivery; that is, consistency and uniformity which are safe, economical and efficient for means of providing the health and wellbeing of mankind. An perfect dosage regimen in the drug therapy of any disease is the one that instantly attains the preferred therapeutic concentration of drug in plasma and maintains it steady for the entire duration of treatment. This is possible through administration of a conventional dosage form in a particular dose and at a particular frequency resulting in a number of limitations. To overcome those limitations effective and safer use of existing drugs through concepts and techniques of modified release and targeted delivery system can result in increased interest. AIM AND OBJECTIVE : The aim and need of this study was directed to develop, optimize and evaluate an efficient CTDDS in two parts. First part deals with budesonide burst release Crospovidone and pH dependent Eudragit L30D coated tablets for ileo caecal targeting to treat mild to moderate CD and in second part budesonide sustained release HPMC K4M and Eudragit L30D coated tablets developed for colonic delivery to treat mild to moderate IBD and for maintenance therapy during disease remission. Budesonide were selected as model standard drugs to treat IBD. Budesonide is a potent, synthetic non-halogenated corticosteroid with high topical anti-inflammatory effect and little systemic effects. Additionally, budesonide has low incidence of adverse effects and high topical effects and has important suggestions in the pharmacotherapy of IBD, both in treatment of UC and CD. It was found that less than 5% of drug was available beyond the ileum and cecum, and hence, colonic delivery still needs to be optimized by a more reliable targeted system. In the present research it was therefore decided to determine whether better formulations for colonic delivery could be formulated as coated with pH sensitive polymer with burst release of budesonide and sustained release budesonide tablets has advantages of bioavailability of high drug concentration at targeted site, reduction in dosage regimen and moreover controlling drug release respectively. The following objectives were outlined to achieve the aim and need of the study: 1. To select appropriate drug and polymers to formulate two colonic delivery systems to treat CD and IBD i.e. a burst immediate release and a sustained release system, both coated with pH dependant solubility profiles to achieve lag time of 5h respectively, 2. To perform Preformulation studies, 3. To develop budesonide loaded tablets with Crospovidone and based on coating with Eudragit L30D, 4. To develop a budesonide loaded tablets with HPMC K4M and based on coating with Eudragit L30D, 5. To perform in vitro release studies & other evaluation parameters for both formulations, 6. Optimization of both formulations, 7. Stability study of both optimized formulations, 8. To perform in vivo animal studies to perform site specificity by Xray imaging and establish pharmacokinetic parameters. MATERIALS AND METHODS : Budesonide was a kind gift from Ethypharma Pvt. Ltd. (Mumbai, India). Eudragit L30D was purchased from the Research-Lab Fine Chem Industries (Mumbai, India). Polyethylene Glycol was purchased from Clariant Pvt. Ltd. (Mumbai, India). Magnesium Stearate, lactose, polyvinyl pyrolidone (PVP K30), Methylene chloride were purchased from Signet India Pvt. Ltd, Mumbai. HPMC K4M, Crospovidone and Isopropyl alcohol (IPA) were purchased from Loba Chemicals (Mumbai, India). Other excipients used were of standard pharmaceutical Grade. Compatibility study of budesonide pure drug, excipients and its physical mixture was evaluated. Melting point of drug was determined using melting point apparatus using capillary method. The calibration curves of budesonide were measured in distilled water, 0.1N HCl and phosphate buffers of 6.8 and 7.4 pH. Compatibility study of budesonide pure drug, excipients and its physical mixture was evaluated. Solubility determination and melting point of drug was determined using melting point apparatus using capillary method. The reported analytical method in methanol was tried by using UV spectrophotometer. RESULT : Compatibility study of budesonide pure drug, excipients and its physical mixture was evaluated and passed as per standards. The melting point of budesonide was determined by using capillary method and was found to be 241-245°C (Standard 245-255°C) which complies with the reported value. The calibration curves of budesonide were measured in distilled water, 0.1N HCl and phosphate buffers of 6.8 and 7.4 pH which showed good linearity with the regression coefficient (R2) as 0.997, 0.998, 0.999 and 0.999 respectively. Budesonide was loaded with Crospovidone and tablets were effectively coated with successive layers of Eudragit L30D on preliminary trial basis. The process had an efficiency of ~90% and ~90–95% in polymeric coating. Compatibility study of budesonide pure drug, excipients and its physical mixture was evaluated and passed as per standards. The melting point of budesonide was determined by using capillary method and was found to be 241-245°C (Standard 245-255°C) which complies with the reported value. CONCLUSION : From the present study it was concluded that, the budesonide pH dependant burst release might be successful preference for ileo-cecal targeting by achieving the desired lag time to treat CD effectively. Also budesonide pH dependant sustain released optimized formulation could be best choice for colon targeted drug delivery by achieving the desired lag time. Satisfactory results were found from evaluation of micromeritic parameters such as flow property, in vitro dissolution study and kinetic study

FORMULATION AND EVALUATION OF VENLAFAXINE HYDROCHLORIDE SUSTAINED RELEASE MATRIX TABLET

Aim: The term modified-release drug product is used to describe products that alter the timing and/or the rate of release of the drug substance.Objective: The objective of the present study was to formulate and evaluate the sustained release matrix tablet of venlafaxine hydrochloride.Methods: Venlafaxine hydrochloride is a structurally novel antidepressant for oral administration. It is widely prescribed for the treatment of depression, generalized anxiety disorder, and social anxiety disorder. Venlafaxine hydrochloride is currently available as immediate release tablet and as an extended release capsules under the brand names of Effexor (WYETH AYERST) and Effexor XR (WYETH AYERST). The biological half-life of venlafaxine very short (5 h) and the dose is to be taken 2–3 times a day and the recommended maximum daily dose is 75–450 mg/day. Venlafaxine hydrochloride is an antidepressant and so it is to be taken for quite a long period. Hence, to reduce the dosing frequency, simple, lower cost sustained release tablets of venlafaxine were preferred for the development.Conclusion: The venlafaxine hydrochloride sustained release matrix tablets shown controlled release profile as per the release profile ofthe innovator is EffexorTm_XR. The sustained release of this matrix tablet reduces the dosing frequency and reduces the side effects, bywhich in a long-term therapy, it may be useful as a product with patient compliance for the treatment of major depression disorder

FORMULATION AND EVALUATION OF CHITOSAN NANOPARTICLES FOR IMPROVED EFFICACY OF ITRACONAZOLE ANTIFUNGAL DRUG

Objective: The main objective of the study was to formulate and evaluate the chitosan nanoparticles to improve the therapeutic efficacy of itraconazole by loading in nanoparticle drug delivery system. Designing the formulation of the drug itraconazole prolongs the therapeutic concentration of the drug in the blood and which will lower the frequency of dosing and also improves the efficacy of the drug. Methods: Itraconazole nanoparticles are prepared by ionic gelation method; here, chitosan is used as polymer. The formulated nanoparticles are evaluated for external morphological studies by scanning electron microscope (SEM), drug content, in vitro drug release studies, as well as infrared (IR) spectral analysis. Results: The Fourier transform IR spectra show that there was no interaction between drug and polymers; hence, they are compatible. Percentage entrapment efficiency, drug content, and percentage yield were higher for F3 formulation. The particle size analysis shows that every particle in the formulations gave the range of 148–227 nm, respectively; increasing in the particle size observed with varying concentration of polymer. SEM analysis of the nanoparticles shows that all the formulations were spherical and smooth with ideal surface morphology. As the concentration of polymer, the drug release decreased proportionally. The stability studies were carried out on the optimized formulation for 2 months at 30±2°C and 60±5% RH and 40±2°C and 75±5% RH; finally, it was observed that there was no change in drug content and in vitro drug release profile even after storage at 30±2°C and 60±5% RH and 40±2°C and 75±5% RH for 2 months. Conclusion: Itraconazole is one among the most widely used antifungal drugs. Designing the formulation of drug itraconazole prolongs therapeutic drug concentration in the blood and decreases dosage frequency and also enhances the efficacy of drug

Estimation of levels of vitamin E in grade II & III haemorrhoids: A prospective study

Objective: The aim and objective of the study is to estimate the levels of vitamin E in blood in grade II & III haemorrhoid patients. Methods: This study was a prospective observational study carried out in Chennai private hospital for a period of 4 months. Institutional Ethical Committee (VISTAS-SPS/IEC/VII/2020/06) approval was obtained before conducting the study. A total of 70 subjects were enrolled based on the inclusion and exclusion criteria and were randomized into 2 groups Group 1 includes healthy volunteers and Group 2 includes haemorrhoid patients. By observing the vitamin E levels in both the groups, the role of vitamin E in haemorrhoids is determined. Results: In total, 70 patients were randomized into Group 1 and Group 2 with 35 patients each. Among 70 patients 40 patients were males and 30 patients were females. In that 18 patients in age group 18-25 years, 26 patients in age group 26-35 years, 20 patients in age group 36-45 years and 6 patients were above 45 years of age.&nbsp

Formulation and Evaluation of Gastro Retentive Drug Delivery System of Candesartan Cilexetil

It had became a challenging experience and effort for a formulator to develop and innovate a drug with maximum bioavailability. In the present study the focus of research is in the treatment of  Hypertension, which  is one of the most prevalent cardiovascular diseases in the world, affecting a big proportion of the adult and old age population. Candesartan Cilexetil angiotensin II to AT1 in many tissues including vascular smooth muscle and the adrenal glands, used for the treatment of high blood pressure. The drug has poor bioavailability due to limited oral absorption and maximum absorption at proximal intestine. This warrants and offers  the use of Gastro Retentive Drug Delivery System (GRDDS) for sustained release formulation in order to achieve prolonged action and to improve patients compliance. Wet granulation technique was selected for preparation of tablets and the drug is formulated with HPMC K100M, ethylcellulose, sodium bicarbonate, Micro crystalline cellulose, Gelucire, talc  and Aerosil etc. For around twelve formulations were made and evaluated for General appearance,  Thickness, Hardness or Crushing strength Test, Friability Test, Estimation of drug content, In-vitro buoyancy studies and In-vitro drug release and the results obtained for the performed tests were found with in the range specified limits

Formulation and evaluation of gastroretentive drug delivery system of eprosartanmesylate

It had became a challenging experience and effort for a formulator to develop and innovate a drug with maximum bioavailability. Objective: In the present study the focus of research is in the treatment of  Hypertension, which  is one of the most prevalent cardiovascular diseases in the world, affecting a big proportion of the adult and old age population. Eprosartan mesylate(EPM)  is angiotensin-II receptor antagonist used for the treatment of high blood pressure. The drug has poor bioavailability due to limited oral absorption and maximum absorption at proximal intestine. This warrants and offers  the use of Gastro Retentive Drug Delivery System (GRDDS) for sustained release formulation in order to achieve prolonged action and to improve patients compliance. Method: Wet granulation technique was selected for preparation of tablets and the drug is formulated with hydroxyl propyl methyl cellulose K100m, hydroxyl propyl methyl cellulose K15m, polyox WSR coagulant, polyox WSR301,polyox WSR N80,  Lactose Monohydrate, Micro crystalline cellulose(Avicel), magnesium sterate, ethylcellulose, sodium bicarbonate, tromethamine, etc. Results:  For around twenty formulations were made and evaluated for General appearance,  Thickness, Hardness or Crushing strength Test, Friability Test, Estimation of drug content

Formulation and evaluation of gastro retentive drug delivery system of candesartan cilexetil

It had became a challenging experience and effort for a formulator to develop and innovate a drug with maximum bioavailability. In the present study the focus of research is in the treatment of  Hypertension, which  is one of the most prevalent cardiovascular diseases in the world, affecting a big proportion of the adult and old age population. Candesartan Cilexetil angiotensin II to AT1 in many tissues including vascular smooth muscle and the adrenal glands, used for the treatment of high blood pressure. The drug has poor bioavailability due to limited oral absorption and maximum absorption at proximal intestine. This warrants and offers  the use of Gastro Retentive Drug Delivery System (GRDDS) for sustained release formulation in order to achieve prolonged action and to improve patients compliance. Wet granulation technique was selected for preparation of tablets and the drug is formulated with HPMC K100M, ethylcellulose, sodium bicarbonate, Micro crystalline cellulose, Gelucire, talc  and Aerosil etc. For around twelve formulations were made and evaluated for General appearance,  Thickness, Hardness or Crushing strength Test, Friability Test, Estimation of drug content, In-vitro buoyancy studies and In-vitro drug release and the results obtained for the performed tests were found with in the range specified limits

Novel approaches of gastro retentive drug delivery system: A review

Oral route of drug administration is the most convenient route and accepted route of drug delivery. It is probable that at least 90% of all the drugs given by oral route. There are different drug deliveries to cure the diseases through oral route. Among them Gastroretentive drug delivery system plays an important and significant role in novel drug delivery systems. The floating systems, bioadhesive drug delivery system, expandable drug delivery system, high density systems, effervescent systems (Gas Generating systems), non-effervescent systems etc are  various approaches. The wide applications can be achieved through this delivery system are enhanced bioavailability, sustained drug delivery, site-specific drug delivery, absorption enhancement, mitigating adversity at colon etc.   In addition to specified above, the advantages and disadvantages, drugs and polymers used and the method of evaluation is also summarized in this review

Formulation and Evaluation of Gastroretentive Drug Delivery System of Eprosartanmesylate

It had became a challenging experience and effort for a formulator to develop and innovate a drug with maximum bioavailability. Objective: In the present study the focus of research is in the treatment of  Hypertension, which  is one of the most prevalent cardiovascular diseases in the world, affecting a big proportion of the adult and old age population. Eprosartan mesylate(EPM)  is angiotensin-II receptor antagonist used for the treatment of high blood pressure. The drug has poor bioavailability due to limited oral absorption and maximum absorption at proximal intestine. This warrants and offers  the use of Gastro Retentive Drug Delivery System (GRDDS) for sustained release formulation in order to achieve prolonged action and to improve patients compliance. Method: Wet granulation technique was selected for preparation of tablets and the drug is formulated with hydroxyl propyl methyl cellulose K100m, hydroxyl propyl methyl cellulose K15m, polyox WSR coagulant, polyox WSR301,polyox WSR N80,  Lactose Monohydrate, Micro crystalline cellulose(Avicel), magnesium sterate, ethylcellulose, sodium bicarbonate, tromethamine, etc. Results:  For around twenty formulations were made and evaluated for General appearance,  Thickness, Hardness or Crushing strength Test, Friability Test, Estimation of drug content

Estimation of Levels of Vitamin E in Grade II & III Haemorrhoids: A Prospective Study

Objective: The aim and objective of the study is to estimate the levels of vitamin E in blood in grade II & III haemorrhoid patients. Methods: This study was a prospective observational study carried out in Chennai private hospital for a period of 4 months. Institutional Ethical Committee (VISTAS-SPS/IEC/VII/2020/06) approval was obtained before conducting the study. A total of 70 subjects were enrolled based on the inclusion and exclusion criteria and were randomized into 2 groups Group 1 includes healthy volunteers and Group 2 includes haemorrhoid patients. By observing the vitamin E levels in both the groups, the role of vitamin E in haemorrhoids is determined. Results: In total, 70 patients were randomized into Group 1 and Group 2 with 35 patients each. Among 70 patients 40 patients were males and 30 patients were females. In that 18 patients in age group 18-25 years, 26 patients in age group 26-35 years, 20 patients in age group 36-45 years and 6 patients were above 45 years of age.&nbsp