Manoj Kumar Vadlamudi | VIT University (original) (raw)

Uploads

Papers by Manoj Kumar Vadlamudi

Nowadays most of the drug substances are coming into the innovation pipeline with poor water solu... more Nowadays most of the drug substances are coming into the innovation pipeline with poor water solubility. Here, the influence of excipients will play a significant role to improve the dissolution of poorly aqueous soluble compounds. The drug substance needs to be dissolved in gastric fluids to get the better absorption and bioavailability of an orally administered drug. Dissolution is the rate-controlling stage for drugs which controls the rate and degree of absorption. Usually, poorly soluble oral administrated drugs show a slower dissolution rate, inconsistent and incomplete absorption which can lead to lower bioavailability. The low aqueous solubility of BCS class II and IV drugs is a major challenge in the drug development and delivery process. Several technologies have been used in an attempt to progress the bioavailability of poorly water-soluble drug compounds which include solid dispersions, lipid-based formulations, micronization, solvent evaporation, co-precipitation, ordered mixing, liquid-solid compacts, solvent deposition inclusion complexation, and steam aided granulation. In fact, most of the technologies require excipient as a carrier which plays a significant role in improving the bioavailability using Hypromellose acetate succinate, Poloxamer. Mesoporous silica and so on. This review deliberates about the excipients significance on bioavailability enhancement of drug products in a single platform along with pragmatically proved applications so that user can able to select the right excipients as per the molecule.

A simple stability-indicating RP-HPLC method was developed and validated for quantification of am... more A simple stability-indicating RP-HPLC method was developed and validated for quantification of
amlodipine, atorvastatin, and its impurities on Waters HPLC using Unisol C18 5 μm, 250 � 4.6 mm column
in their combined tablet dosage as per ICH guidelines. The gradient (T/%B) at 0/42, 18/42, 22/75, 30/75,
32/42, and 35/42 of 40 mM 4.7 pH ammonium acetate as mobile phase A and acetonitrile as mobile
phase B of flow rate 1.5 mL/min and 240 nm wavelength. Peak purity compiled for amlodipine and
atorvastatin in all stressed conditions. For impurities: Precision was found in between 1.5 and 3.6%. The
limit of detection and quantification for amlodipine, amlodipine impurity A, and atorvastatin was
found to be 0.06 and 0.18 μg/mL, for atorvastatin Impurity A, B, C, and H was determined as 0.04 and
0.11 μg/mL, for Atorvastatin Impurity D was measured as 0.11 and 0.28 μg/mL, respectively. The linear
regression achieved >0.9999 from 0.22 to 7.5 μg/mL. Recovery was observed in between 97 and 101%.
For assay: Precision was determined in between 0.1 and 0.2%. The linear regression achieved >0.9999 for
amlodipine and atorvastatin. Recovery ranged from 100 to 101%. The validated method was found to be
accurate, precise, reliable, and robust to determine the assay as well as impurities in amlodipine–
atorvastatin combination dosage formulation.

Abstract Background: Methods were not available in the monographs like United States Pharmacopeia... more Abstract
Background: Methods were not available in the monographs like United States Pharmacopeia, British
pharmacopeia and European pharmacopeia and also in the literature for the determination of three related impurities
namely Impurity A, B and C in Felodipine solid dosage form with a shorter runtime using RP-HPLC.
Method: A simple RP- HPLC method was developed and validated for the quantification of Felodipine Impurity
A, B and C in Felodipine solid dosage form and in drug substance. This method was developed on waters alliance
using Phenomenex Gemini column C18 5 μm,150 × 2.0 mm i.d, using the isocratic program with the mobile phase
ratio of 0.02 mM ammonium acetate adjusted to pH 5 and acetonitrile (55:45,v/v) with a flow rate of 0.7 mL/min. The
λmax is at 240 nm.
Results: Forced degradation was performed as per ICH guidelines and no interference of the impurities with
the known peaks was found. Precision was found between 0.1 and 0.2%. The Limit of detection and quantification
for Felodipine and impurity A; Impurity B and C were 0.05 and 0.15 μg/mL respectively. The linearity correlation
coefficient was found to be >0.999 for Impurity A and Felodipine; Impurity B and C of concentration range 0.2-30.0
μg/mL and 0.2-8.0 μg/mL respectively. The method accuracy was assessed for Felodipine and its impurities at four
levels (LOQ, 50%, 100% and 150%) and the recovery ranged from 95% to 106%.
Conclusion: The method was found to be precise, reliable, accurate and robust.

Bioavailability is the rate and extent to which the active ingredient or active moiety is absorbe... more Bioavailability is the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. Traditionally, nearly 40% of the new chemical entities (NCEs) identified by pharmaceutical industry screening programs have failed to be developed due to of poor water solubility, which makes their formulation difficult or even impossible to come into the regular market. Solubility is one of the important ways to achieve the desired concentration of drug in to the systemic circulation for its pharmacological response and also most of the drugs are weakly acidic and weakly basic with poorly aqueous solubility. The oral route of administration is the most preferred and widely acceptable route of delivery due to ease of ingestion for many drugs, however these drugs with slow dissolution rate and low solubility in aqueous media shows the incomplete absorption leading to low bioavailability when orally administered. Poorly aqueous soluble drugs often require high doses in order to reach therapeutic plasma concentrations of oral concentration because of which increase in the side effects for certain drugs. Pharmaceuticals falling under the Biopharmaceutics Classification System (BCS) class II and IV are the main emphasis of this review as these drugs are of low solubility. Here we discussed about traditional techniques, novel drug delivery technologies, solid dispersion techniques and vascular approaches to enhance the solubility as well as the bioavailability of low soluble drugs.

Analytical method should be developed as stability indicating and validate to provide reliable da... more Analytical method should be developed as stability indicating and validate to provide reliable data for regulatory submissions. Analytical method is establishing evidence that provides a high degree of assurance and is an important process in the drug discovery. Even though the drug shows good potency, lack of a validated analytical method will not allow the drug to enter into regular analysis as well as in the market. This review covers the importance/practical way of development, forced degradation and validates stability indicating analytical method and their strategies along with brief knowledge of analytical chromatographic parameters needs to be optimized of an effective method development for drug substance as well as produc

Objective: The present paper reports the development of simple, rapid, accurate and stability ind... more Objective: The present paper reports the development of simple, rapid, accurate and stability indicating reversed phase high-performance liquid chromatography method (RP-HPLC) for estimation of related substances in Atorvastatin calcium (ATV) bulk drug as well as in solid dosage form. The method was validated using Agela, Unisol C18 (250 mmX 4.6 mm; 5µ) column. Methods: A method was developed to separate clearly the drug peak from the synthetic/process impurities and degradation products formed under stress conditions is attained on (T/%B) were set at 0/43, 18/43, 20/60, 33/60, 35/43, and 40/43 of 0.02 mM ammonium acetate buffer of pH4.9 was used as mobile phase A and 90:10 v/v, ratio of acetonitrile and tetrahydrofuran was used as mobile phase B. A flow rate of 1.4 ml/min and column temperature of 25 °C was used. The wavelength selected was 246 nm. The developed method was validated as per ICH guidelines for the specificity, precision, linearity, accuracy, limit of detection, limit of quantitation and robustness. Results: Linearity of the impurities was accomplished in the range 0.3-6.0µg/ml for impurity A (Imp A), B (Imp B), C (Imp C), H (Imp H) and 0.4-6.0µg/ml for impurity D (Imp-D), correlation coefficient was found to be more than 0.999 for all impurities. Recovery of impurities was found to be in the range 93%-111%. Conclusion: The developed method was simple, precise, accurate, robust and also cost effective as it has shorter run time for quantification of impurities in drug substance and drug product as well.