Amneal (United States)

The pharmaceutical industry is undergoing a significant transformation driven by the integration of digital technologies, collectively known as Industry 4.0. This shift is redefining how drugs are developed, manufactured, and distributed. Key technologies such as the Internet of Things (IoT), Artificial Intelligence (AI), and big data analytics are at the forefront of this change, enabling smart manufacturing, real-time process optimization, and enhanced supply chain management. IoT facilitates the creation of interconnected production environments where sensors and devices continuously monitor critical parameters, ensuring optimal conditions and predictive maintenance. AI accelerates drug discovery through predictive modeling, automates quality control processes, and employs predictive analytics to enhance maintenance and process improvement. Big data empowers data-driven decision-making, ensures regulatory compliance through comprehensive analysis, and supports the shift toward personalized medicine by enabling customized drug production. Despite the significant benefits, the adoption of these technologies poses challenges, including integration with existing systems, data security concerns, and navigating a complex regulatory landscape. This review explores these technologies' impact on pharmaceutical manufacturing, highlighting successful case studies and best practices. Additionally, it discusses the future directions, including the move towards fully autonomous systems and the importance of collaboration between tech companies, manufacturers, and regulators to drive innovation and ensure compliance. The continued evolution of digital technologies in pharma manufacturing promises to enhance efficiency, reduce costs, and deliver more personalized treatments.

Montelukast sodium (MLS) is a leukotriene receptor antagonist that relieves asthma, bronchospasm, allergic rhinitis, and urticaria. A simple, robust, and stability-indicating normal phase high-performance liquid chromatography method was developed to separate and quantitatively estimate the S-enantiomer of MLS. The chiral separation was achieved using USP L51 packing material along with a mobile phase consisting of a solvent mixture (n-hexane, ethanol, and propionic acid), a flow rate of 1.0mL/min, a detection wavelength of 284 nm, a column temperature of 30°C and an injection volume of 20 μL. The enantiomers peaks were well separated from the peaks of the placebo, diluting solvent, MLS, and its known impurities with a resolution of more than 2.2 and with no interference. Accuracy and linearity were studied in a range of 0.36-3.597 μg/mL (0.03%-0.30%), with good recoveries between 92.5% and 96.8% and a linear regression coefficient above 0.996. The suggested chiral chromatography method is being considered as an alternative and equivalent method to the United States Pharmacopeia and European Pharmacopeia monographs. The developed method was effectively employed for the study of release and stability samples of MLS. This HPLC method is also capable of separating and estimating the stereo-selective isomers (R- and S-enantiomers) of sulfoxide impurity of MLS in pharmaceutical medicine.

To evaluate the efficacy and safety of zolmitriptan nasal spray (ZNS) in the acute treatment of migraine headache in patients aged 6 to 11 years. Triptans have demonstrated efficacy in adults, but pediatric studies of these agents have largely failed and there are few triptan options for these patients. Because lack of response to 1 triptan does not necessarily preclude response to an alternate triptan, additional triptan options for pediatric patients are desirable. This Phase 3, randomized, double-blind, placebo-controlled, multicenter crossover trial with an open-label extension enrolled patients aged 6 to 11 years with a diagnosis of migraine for ≥6months and ≥16 headache-free days/month (N=373). After a run-in period to eliminate placebo responders, 186 patients were randomized within their body weight stratum to ZNS followed by matching placebo, or placebo followed by matching ZNS. Patients <50 kg who were randomly allocated to ZNS were randomized to 5:1 to ZNS 2.5 or 1.0mg; those ≥50 kg were randomized 5:1 to ZNS 5.0 or 2.5mg. Patients had 6 weeks to treat 1 moderate to severe migraine headache and then crossed over to the alternate arm, during which they had 6 weeks to treat a second migraine attack. Patients could participate in a subsequent 6-month outpatient open-label extension. The primary efficacy endpoint was pain-free status at 2h in patients treated with the high dose from each stratum. The trial was terminated early due to slow enrollment. Three hundred patients (mean age, 9 years) entered the placebo run-in period and 186 entered the double-blind period. Pain-free status at 2h postdose was achieved by 45/133 (33.8%) and 30/128 (23.4%) of patients who received high-dose ZNS and placebo, respectively (p=0.0777; odds ratio [OR] 1.51; 95% confidence interval [CI] 0.96, 2.38). Several secondary endpoints achieved statistical significance. There were few treatment-related adverse events and none led to discontinuation. ZNS retained efficacy and demonstrated a consistent safety profile throughout the 6-month open-label extension. The effect of high-dose ZNS on the primary endpoint of pain-free status at 2h did not achieve statistical significance. ZNS was safe and well tolerated in this pediatric population.

The principle motive behind this work is to develop robust, low cost, and regulatory flexible method for Tadalafil and Macitentan by RP-HPLC using Analytical Quality by Design principles. Failure Mode and Effects Analysis was performed and the risk priority number was calculated, from this analysis independent variables were selected. Optimization of chromatographic condition was performed using Central Composite Design. The separation was achieved using phenomex gemini C18 (150 mm, 4.6 mm, 5μm) column using mobile phase as methanol: 10 mM ammonium formate (74.1 : 25.9 % v/v) (pH: 6.8) at a flow rate 0.94 ml/ min with detection wavelength at 260 nm and 40°C column oven temperature. This method was validated according to ICH Q2 (R1) guideline. Analytical Quality by Design method was numerically optimized with a desirability of 1.0. ANOVA result shows that model was significant for all responses. The method was found to be linear in the range of 0.1-25 μg/ml for Macitentan and 0.4-100 μg/ml for Tadalafil. Percentage recovery was found in the range of 98.6-101.7 % for Macitentan and 98.8-101.8 % for Tadalafil. The RSD of precision and repeatability was found beneath 1 %. AQbD driven method can be highly suitable for analysis of Tadalafil and Macitentan without interference.

This research study aimed at developing and validating a simple, precise, accurate, specific and economical spectrophotometric method for simultaneous estimation of Ranolazine (RANO) and Metformin hydrochloride (MET) in synthetic mixture. This method is based on first order derivative spectroscopy.Ranolazine and Metformin hydrochloride exhibited absorbance at working wavelength 232.86 nm (Zero crossing point of Metformin hydrochloride) and 249.29 nm (zero crossing point of Ranolazine) respectively using water as a diluent. This method was validated as per ICH guideline. Linearity was established over the concentration range of 2-35 μg/mL both of Ranolazine and Metformin hydrochloride with correlation coefficients 0.999 and 0.998, respectively. Accuracy was obtained between 98.48-101.85% and 98.25-100.88% for Ranolazine and Metformin hydrochloride respectively. LOD and LOQ were found to be 0.08 μg/mL and 0.25 μg/mL for Ranolazine and 0.25 μg/mL and 0.77 μg/mL for Metformin hydrochloride, respectively.The results revealed that, the developed method was suitable for the routine analysis of determination of Ranolazine and Metformin hydrochloride in combine dosage form. Keywords: Ranolazine; Metformin hydrochloride; First order derivative; UV spectrophotometry; ICH guideline

The most common pharmaceutical dosage forms for topical delivery of drugs are creams, ointments, and gels, all of which are semisolid in consistency. Attributes that are critical to the effective performance of pharmaceutical semisolids include viscosity, API status, and bioavailability and shelf-life stability. Recent investigations have demonstrated that these critical attributes are driven by the microscale organization of matter (or microstructure) in the semisolid formulation. The microstructure is, in turn, affected by the selection of excipients, amount of excipients, quality of excipients, as well as the processing methods utilized to manufacture the semisolid product. This chapter explores the role of excipients in the microstructure of creams, ointments, and gels, as well as the impact of microstructure on their critical quality attributes and performance.

Transdermal drug delivery systems (TDDS) are used for the delivery of the drugs through the skin into the systemic circulation by applying them to the intact skin. The development of TDDS is a complex and multidisciplinary affair which involves identification of suitable drug, excipients and various other components. There have been numerous problems reported with respect to TDDS quality and performance. These problems can be reduced by appropriately addressing chemistry, manufacturing and controls requirements, which would thereby result in development of robust TDDS product and processes. This article provides recommendations on the chemistry, manufacturing and controls focusing on the unique technical aspects of TDDS.