Beyond Commodity Excipients: A Strategic Roadmap for Advanced Pharmaceutical Materials in Iran

The pharmaceutical raw-material industry is undergoing a structural change. For decades, the conventional distinction was relatively simple: active pharmaceutical ingredients on one side and excipients such as binders, coatings, fillers, disintegrants and stabilizers on the other. That distinction is becoming increasingly inadequate.

In many modern formulations, an excipient is no longer a chemically passive ingredient. A polymer may determine whether a poorly soluble drug becomes bioavailable. Another may control whether an injectable product releases its active ingredient over one month or six months. A highly purified surfactant may determine the long-term stability of a monoclonal antibody, while an ionizable lipid can determine whether an RNA molecule reaches the cytoplasm at all.

The strategic question for countries with established generic pharmaceutical industries is therefore changing.

The issue is no longer simply:

Which imported pharmaceutical raw materials can be manufactured locally?

A more consequential question is:

Which pharmaceutical materials are becoming technologically indispensable to the next generation of medicines, and in which of those materials can a country realistically build a defensible industrial position?

This distinction matters particularly for Iran. A broad pharmaceutical manufacturing base does not automatically translate into technological depth in pharmaceutical materials. Import substitution may reduce vulnerability in selected products, but attempting to localize every imported chemical is neither economically rational nor technologically strategic.

The more promising direction is to move gradually from commodity pharmaceutical raw materials toward functional pharmaceutical materials: materials whose reproducibility, impurity profile, molecular architecture and performance directly affect the critical quality attributes of the final medicine.

Among the candidates for such a transition, PLGA deserves particular attention. Yet it should not be considered in isolation. Copovidone, HPMCAS, sulfobutylether-β-cyclodextrin, high-purity biopharmaceutical surfactants and, over a longer horizon, lipid nanoparticle components may collectively define a more realistic technology ladder.

The challenge is not to pursue all of them simultaneously. It is to determine the right sequence.

PLGA: an old polymer, but not a simple one

Poly(lactic-co-glycolic acid), or PLGA, is among the best-established biodegradable polymers used in controlled drug delivery.

It has been incorporated into microspheres, implants and long-acting injectable formulations for several decades. Approved PLGA-based medicines have been used in prostate cancer, endocrine disorders, psychiatric disease, substance-use disorders, ophthalmology and other therapeutic areas. Depending on the formulation, drug release can extend from several weeks to several months.

This long clinical history can create a misleading impression that PLGA is now a mature and relatively straightforward pharmaceutical material.

It is not.

A key point is that PLGA is not one material but a family of materials.

The lactide-to-glycolide ratio is only one determinant of performance. Molecular weight, molecular-weight distribution, intrinsic viscosity, end-group chemistry, initiator, polymer architecture, monomer sequence distribution, residual monomers, residual catalyst, residual solvents and batch-to-batch consistency can all influence degradation and drug release.

Two materials both labelled “PLGA 50:50” may therefore behave differently in the same dosage form.

This distinction is central to investment decisions. A manufacturer capable of polymerizing lactide and glycolide is not necessarily capable of producing pharmaceutical-grade PLGA suitable for a complex long-acting injectable.

The difficulty lies in controlling function, not merely composition.

Japan provides the clearest historical lesson

The development of leuprolide long-acting formulations by Takeda is one of the most instructive cases in pharmaceutical polymer development.

In the 1980s, Japanese researchers including Yasuaki Ogawa and Hiroaki Okada investigated how the molecular weight and lactide-to-glycolide ratio of biodegradable polymers affected the release of leuprolide acetate.

Their work did not begin with a business plan to manufacture PLGA as a raw material.

It began with a therapeutic problem:

How could a drug requiring frequent administration be converted into a sustained-release injectable?

The polymer was subsequently optimized around the product.

That pathway eventually contributed to the development of Lupron Depot and subsequent one-, three-, four- and six-month formulations.

The industrial lesson is fundamental.

A successful PLGA strategy should preferably be product-driven rather than polymer-driven.

The objective is not to make PLGA and later search for applications. The objective is to define the required pharmacokinetic profile of a medicine and then engineer the polymer and manufacturing process to achieve it.

This principle should shape any serious PLGA investment strategy.

The Swiss experience shows how specialized PLGA can become

Sandostatin LAR, originally developed by Sandoz and subsequently marketed by Novartis, illustrates an even higher level of polymer complexity.

Its long-acting octreotide formulation uses a branched, glucose-initiated PLGA system rather than a simple linear copolymer.

Research involving the U.S. Food and Drug Administration has shown that conventional polymer measurements such as average molecular weight and lactide-to-glycolide ratio may be insufficient to establish structural equivalence for such materials. Specialized analytical methods were required to characterize branching and molecular architecture.

The implication is important for new entrants.

At the upper end of the PLGA market, competition is not simply between polymerization facilities. It is between accumulated bodies of knowledge linking:

polymer architecture,

manufacturing conditions,

particle morphology,

drug loading,

degradation kinetics,

and in-vivo release.

This creates a substantial barrier to entry.

It also creates value for manufacturers that can cross that barrier.

The U.S. generic experience demonstrates the difficulty

Perhaps the strongest evidence of PLGA complexity comes from the U.S. generic-drug pathway.

Risperdal Consta was approved in 2003. Sandostatin LAR had been available even earlier.

Despite large commercial incentives to develop lower-cost generic versions, the FDA reported that the first PLGA-based generic equivalents to these complex long-acting products were not approved until December 2023.

The long delay was not mainly the result of an inability to manufacture polymer.

The regulatory problem involved demonstrating equivalence in polymer characteristics, microsphere structure, manufacturing process, in-vitro drug release and ultimately therapeutic performance.

FDA research has continued into characterization methods, release testing and in-vitro/in-vivo relationships for these products.

This is an unusually important warning for industrial policy.

A PLGA project should not be classified simply as a specialty-polymer project.

At meaningful pharmaceutical sophistication, it belongs at the intersection of:

materials science, formulation science, analytical science and regulatory science.

Even identical ingredients may not produce identical products

In complex long-acting injectables, qualitative and quantitative formulation sameness does not necessarily guarantee functional sameness.

Manufacturing variables can strongly affect microsphere characteristics.

Solvent-removal rate, temperature, mixing conditions, polymer concentration, droplet formation, particle hardening and drying can change particle size, internal porosity, drug distribution and release kinetics.

Research involving FDA scientists has shown that even the source of the PLGA polymer can affect in-vitro and in-vivo behaviour.

This means a pharmaceutical customer is not simply purchasing a certificate of analysis.

The customer needs confidence that switching from one PLGA source to another will not destabilize a formulation that may have taken years to develop.

That creates a high switching cost.

For a new supplier this is initially a disadvantage. Once successfully qualified, however, it can become a competitive advantage because customers are unlikely to change suppliers casually.

The appropriate commercial strategy is therefore not simply to undercut established PLGA suppliers on price.

It is to become involved during formulation development and qualification.

PLGA should enter Iran through a narrow technology platform, not a large plant

If PLGA is pursued, the initial objective should not be a broad catalogue of products.

A more rational first stage would concentrate on a limited number of pharmaceutical-grade linear PLGA grades, for example:

PLGA 50:50,

PLGA 75:25,

selected acid-terminated grades,

selected ester-terminated grades,

and perhaps two or three molecular-weight ranges.

Each additional grade introduces new requirements for synthesis, analytical characterization, stability and application development.

Ten poorly characterized grades are less valuable than three grades that can repeatedly reproduce the same performance.

The first-stage investment should therefore emphasize:

polymerization process control,

purification,

GPC/SEC,

NMR,

DSC,

residual-monomer analysis,

residual-catalyst analysis,

intrinsic-viscosity measurement,

stability studies,

and batch-to-batch reproducibility.

The core question should be whether three consecutive batches truly behave as the same pharmaceutical material.

Only after that question has been answered does large-scale capacity become relevant.

PLGA should be qualified inside a real drug product

The second step should involve collaboration with one or more pharmaceutical manufacturers.

A domestically produced PLGA grade should be evaluated directly against an established international reference material in a real formulation.

Relevant parameters may include:

encapsulation efficiency,

particle-size distribution,

porosity,

initial burst,

in-vitro release,

stability,

and ultimately pharmacokinetic behaviour.

For early technology demonstration, products based on well-understood therapeutic platforms may be more rational than attempting a completely novel formulation.

GnRH analogues such as leuprolide or triptorelin could warrant feasibility assessment because PLGA-based depot formulations in this class have decades of global development history.

This does not mean that either product is automatically commercially appropriate for Iran. Market size, intellectual-property position, competition, formulation capability and regulatory feasibility must all be assessed independently.

The broader principle is more important:

the first PLGA should be developed together with the first drug that needs it.

Risperidone and octreotide should probably come later

Risperidone long-acting microspheres are commercially attractive, but the complexity of the generic-development pathway suggests that they may not be the lowest-risk initial technology demonstrator.

Octreotide LAR is even more demanding because of the specialized branched PLGA architecture used in the reference product.

These are better viewed as second- or third-generation objectives after a domestic platform has demonstrated reliable synthesis, characterization and formulation performance.

The technology ladder matters.

Attempting to begin at the top may convert an ambitious project into a capital-intensive failure.

PLGA is only one part of the opportunity

The broader strategic question is what should come before, alongside and after PLGA.

Five additional material families appear particularly relevant when assessed against four practical criteria:

technological distance from capabilities that can realistically be built in Iran;

established or emerging pharmaceutical demand;

regulatory difficulty;

and

potential for international market differentiation.

On this basis, not all fashionable technologies deserve equal investment priority.

First priority: advanced Copovidone and low-impurity PVP systems

Copovidone, or PVP/VA, is a strong candidate for relatively near-term industrial upgrading.

Its importance has expanded because of the growth of amorphous solid dispersions, one of the major formulation strategies for poorly water-soluble drugs.

A 2024 analysis of FDA-approved amorphous solid-dispersion products between 2012 and 2023 identified 48 products. Copovidone represented approximately 49 per cent of the polymers used, while HPMCAS represented roughly 30 per cent.

This is significant because it is based on actual approved medicines rather than commercial market forecasts.

The opportunity, however, is not ordinary Copovidone.

In an ASD formulation, molecular weight, polymer composition, hygroscopicity, thermal behaviour and drug-polymer interactions influence stability and dissolution performance.

An even more immediate opportunity comes from the regulatory focus on nitrosamines.

FDA and WHO have increased expectations for identifying and controlling nitrosamine risks across APIs, excipients and finished products. Nitrite contamination in excipients can contribute to nitrosamine formation, and published multi-company datasets demonstrate substantial variability in nitrite levels between excipient types, suppliers and batches.

This creates a commercially meaningful distinction between a standard polymer and one supported by:

low nitrite,

low peroxide,

low residual monomer,

defined molecular-weight distribution,

and demonstrated batch consistency.

For a manufacturer with relevant polymer capabilities, this may offer one of the lowest-risk routes into a higher-value pharmaceutical-material segment.

The industrial logic is compelling because much of the additional value comes from process control, purification and analytical capability, rather than necessarily from constructing a very large new chemical complex.

Second priority: HPMCAS and the advanced oral-polymer platform

Hypromellose acetate succinate, or HPMCAS, provides another attractive route.

Japan has a particularly important history in its development and commercialization.

HPMCAS was initially associated mainly with enteric applications, but its role has expanded considerably through amorphous solid-dispersion technology.

It can help stabilize poorly soluble APIs in the amorphous state, maintain supersaturation after dissolution and inhibit recrystallization.

Its relevance to approved medicines is well established.

From an Iranian industrial perspective, HPMCAS appears less technologically distant than advanced PLGA formulations while still offering substantially greater differentiation than common coating polymers.

Its production nevertheless requires careful control of:

acetyl substitution,

succinyl substitution,

methoxy and hydroxypropoxy content,

viscosity,

molecular characteristics,

and pH-dependent behaviour.

Copovidone and HPMCAS should not necessarily be treated as two unrelated businesses.

They can form part of a single advanced oral-polymer and solubility-enhancement platform.

Such a platform could eventually provide not only materials but also application support for:

spray drying,

hot-melt extrusion,

polymer screening,

and formulation selection.

This is a crucial transition.

The manufacturer stops selling only kilograms of polymer and begins selling part of a formulation solution.

Third priority: SBE-β-cyclodextrin

Sulfobutylether-β-cyclodextrin occupies an attractive position between a conventional excipient and a sophisticated drug-delivery material.

Cyclodextrins can form inclusion complexes with hydrophobic molecules and thereby increase solubility or stability. SBE-β-CD has high aqueous solubility and has been incorporated into approved pharmaceutical products, including parenteral formulations.

Its industrial attraction lies in the combination of:

established regulatory precedent,

relatively specialized chemistry,

lower-volume but higher-value demand,

and technical barriers that reduce pure commodity competition.

However, manufacturing quality cannot be judged simply by chemical purity.

The degree and distribution of substitution, residual reagents, purification efficiency and impurity profile are critical. If intended for parenteral use, expectations become significantly more demanding.

For this reason, SBE-β-CD is better suited to a pilot or semi-industrial, customer-linked investment than an immediate large-capacity plant.

Its logical place is after establishment of a strong analytical and high-purity excipient platform.

Fourth priority: biopharmaceutical-grade surfactants

The rise of monoclonal antibodies, recombinant proteins, biosimilars and other biological medicines is creating a distinct market for highly controlled excipients.

Polysorbate 20 and Polysorbate 80 remain widely used to protect therapeutic proteins against interfacial stress and aggregation.

Their weakness is degradation.

Oxidation, hydrolysis and trace host-cell enzymes can degrade polysorbates and contribute to particle formation in biological products.

This has led industry to investigate alternatives, particularly Poloxamer 188.

A 2025 pharmaceutical-industry survey involving companies participating in the International Consortium for Innovation and Quality in Pharmaceutical Development reported that Poloxamer 188 was already present in more than twenty approved biological products, while many companies were developing additional formulations using it.

Still, this should not be interpreted as the imminent disappearance of polysorbates.

Polysorbate 20 and 80 remain deeply embedded in the biopharmaceutical industry.

For Iran, the more immediate commercial opportunity may therefore be high-purity biopharmaceutical-grade polysorbates with tightly controlled degradation-related impurities, while Poloxamer 188 represents a somewhat longer-term platform.

The manufacturing challenge is significant because pharmaceutical-grade block copolymers and ultra-pure surfactants require sophisticated process control and purification.

This field should be developed alongside a real domestic or export-oriented biologics industry.

Without downstream biopharmaceutical demand, the investment case weakens substantially.

Fifth priority: ionizable lipids, but only as an R&D platform for now

Ionizable lipids are arguably the most technologically exciting materials in this portfolio.

They are central to many lipid-nanoparticle systems for mRNA and siRNA delivery.

Small structural modifications can substantially alter:

encapsulation,

biodistribution,

endosomal escape,

potency,

and toxicity.

Their technological value is therefore exceptionally high.

Their near-term industrial investment case is far less straightforward.

A 2025 Nature Nanotechnology perspective involving scientists from major global pharmaceutical companies highlighted the chemistry, manufacturing and control challenges associated with novel lipid excipients. In some circumstances, the regulatory expectations for a new lipid can approach those for an active pharmaceutical ingredient.

This creates substantial cost and uncertainty.

Consequently, it would be difficult to justify immediate construction of a large industrial ionizable-lipid facility in the absence of specific downstream RNA-development programmes.

The more rational strategy is:

gram-to-kilogram synthesis capability,

advanced characterization,

purification and impurity profiling,

collaboration with an mRNA or siRNA developer,

selection of a limited number of lipid candidates,

and only then pilot scale-up.

This is a venture-style technology programme, not yet a conventional manufacturing investment.

Its position at the bottom of the near-term investment ranking should not be confused with low technological value.

In terms of future strategic importance, it may rank among the highest.

In terms of risk-adjusted industrial investment today, it ranks considerably lower.

Where should PLGA sit in the overall ranking?

If PLGA is inserted into the broader portfolio, it sits approximately between HPMCAS/SBE-β-CD and advanced biopharmaceutical surfactants in terms of investment risk.

It is technologically more demanding than advanced oral excipients because commercial success depends heavily on a downstream long-acting formulation.

It is less speculative than novel ionizable lipids because decades of clinical use, established regulatory pathways and multiple approved products already exist.

A simplified order for development could therefore be:

1. Advanced Copovidone/PVP and low-impurity grades

2. HPMCAS and the ASD polymer platform

3. SBE-β-CD

4. PLGA pilot development linked to a specific long-acting injectable

5. Biopharmaceutical-grade surfactants, including high-purity polysorbates and Poloxamer 188

6. Ionizable lipids and other LNP components as an R&D platform

This ordering is not a ranking of scientific importance.

It is a ranking of risk-adjusted industrial logic for the next stage of development.

The key strategic change: build technology platforms, not isolated factories

One of the most damaging approaches would be to create a separate project for every promising material.

Advanced pharmaceutical materials share capabilities.

Copovidone and HPMCAS depend on polymer science, impurity control and formulation understanding.

PLGA and PLA share aspects of biodegradable-polymer chemistry and analytics.

Biopharmaceutical surfactants require common ultra-purification and trace-impurity capabilities.

LNP materials require sophisticated synthetic chemistry and analytical control.

It is therefore more rational to develop technology platforms.

Platform 1: Advanced Oral Polymers

Copovidone,

HPMCAS,

selected specialized PVP/HPMC grades,

ASD-support materials.

Platform 2: Advanced Solubilizers

SBE-β-CD,

selected cyclodextrin derivatives.

Platform 3: Controlled-Release Polymers

PLGA,

PLA,

and later selected PEG-PLGA systems.

Platform 4: Biopharmaceutical Excipients

high-purity polysorbates,

Poloxamer 188,

selected stabilizers.

Platform 5: Nucleic-Acid Delivery Materials

ionizable lipids,

PEG-lipids,

specialized phospholipids.

This approach concentrates analytical talent, application expertise and regulatory knowledge rather than dispersing them across multiple disconnected factories.

In advanced pharmaceutical materials, the laboratory may matter more than the second reactor

Traditional chemical-industry investment often equates growth with additional reaction capacity.

That logic becomes less reliable as pharmaceutical materials become more sophisticated.

The true bottleneck may instead be analytical.

Depending on the material, a competitive platform may require capabilities such as:

GPC/SEC,

NMR,

LC-MS,

GC-MS,

ICP-MS,

ion chromatography,

LC-CAD,

DSC,

TGA,

and application-specific performance testing.

Nitrosamine-related regulations illustrate this shift particularly well.

A standard excipient may become commercially differentiated because one supplier can reliably document nitrite and peroxide levels at concentrations relevant to the drug manufacturer's risk assessment.

Likewise, PLGA value depends not simply on composition but on control of molecular architecture and performance.

In such businesses, an advanced analytical laboratory may create more export value than doubling reactor capacity.

The investment rule should be simple: grade first, capacity second

Across all of these materials, the same principle applies.

Do not build large capacity and then attempt to create a pharmaceutical grade.

Develop the grade first.

A credible early-stage project should answer several questions:

Can three consecutive batches meet the same critical material attributes?

Does the material perform comparably with an established international reference grade?

Can impurity profiles be controlled reproducibly?

Is long-term stability acceptable?

Will a real pharmaceutical customer qualify the material?

Can the process ultimately become cost-competitive at commercial scale?

Only when these questions are answered does capacity expansion become strategically rational.

This sequence is particularly important in Iran, where capital allocation, foreign exchange and specialized equipment cannot be treated as unlimited resources.

Export orientation must begin before commercialization

Advanced pharmaceutical materials cannot be designed exclusively for the domestic market and then retrofitted for export.

The intended market should influence specifications from the beginning.

If eventual customers include manufacturers operating under U.S., European, Japanese or WHO-recognized standards, development batches should already generate information on:

impurity profiles,

residual solvents,

residual monomers,

trace metals,

nitrite and nitrate where relevant,

peroxide,

molecular-weight distribution,

stability,

change control,

and batch variability.

The regulatory dossier should develop alongside the material.

For PLGA and other excipients intended for international pharmaceutical use, Drug Master File strategies may eventually become relevant.

The broader lesson is straightforward.

Regulatory documentation should not be treated as paperwork prepared after production.

It is part of the product.

What should not be done

A disciplined strategy is defined as much by what it rejects as by what it funds.

Several approaches appear particularly weak.

First, do not manufacture a material simply because it is currently imported.

Import dependence alone does not establish economic or technological justification.

Second, do not build a large PLGA plant before pilot qualification.

The product risk is too high.

Third, do not industrialize ionizable lipids solely because RNA therapeutics are growing.

Downstream demand and regulatory feasibility must exist first.

Fourth, do not launch ten advanced-material projects simultaneously.

Analytical and formulation expertise will be diluted.

Fifth, do not confuse pharmacopeial compliance with functional equivalence.

Passing a monograph does not prove that the material will behave identically in a sophisticated formulation.

Sixth, do not increase production capacity before building analytical capacity.

In this sector the laboratory is part of the production technology.

Seventh, do not compete only on price.

A domestic supplier that survives solely because of tariffs or import restrictions has not created a strong technological position.

Eighth, do not separate raw-material development from downstream formulation.

The more sophisticated the material, the more damaging that separation becomes.

A possible development sequence for Iran

A rational technology ladder could proceed in six stages.

Stage 1: Upgrade existing materials

Develop low-nitrite, low-peroxide and tightly specified functional grades of materials already close to existing industrial capabilities.

The objective is to learn high-level impurity control, batch consistency and pharmaceutical documentation.

Stage 2: Build an advanced oral-polymer platform

Develop Copovidone grades for amorphous solid dispersions and then HPMCAS.

Create application capability in spray drying, hot-melt extrusion and polymer screening.

Stage 3: Enter specialized solubilizers

Develop SBE-β-CD and selected high-value cyclodextrin derivatives through pilot production and pharmaceutical qualification.

Stage 4: Establish the PLGA platform

Develop a small number of linear pharmaceutical-grade PLGA materials and link at least one of them to a real long-acting injectable development project.

Only after qualification should GMP commercial capacity be expanded.

Stage 5: Build biopharmaceutical-excipient capability

Move into ultra-high-purity surfactants and stabilizers as domestic biologics capability develops.

Stage 6: Maintain a focused LNP-material R&D programme

Build knowledge in ionizable lipids and related materials before committing to industrial scale.

This should initially be technology acquisition and capability building rather than volume manufacturing.

The final strategic criterion

The ultimate question for every proposed pharmaceutical-material project should not be:

Can it be produced in Iran?

That question is too easy.

The better question is:

If tariffs, import restrictions and administrative protection disappeared tomorrow, would an international pharmaceutical company still have a reason to buy this material from an Iranian manufacturer?

If the only answer is lower price, the competitive position is fragile.

If the answer includes:

reproducible quality,

a differentiated pharmaceutical grade,

a superior impurity profile,

reliable technical documentation,

formulation support,

custom development,

and the ability to solve a specific pharmaceutical problem,

then the project begins to resemble a technology business rather than an import-substitution factory.

That distinction should guide the next stage of pharmaceutical-material investment.

The strategic opportunity is not merely to manufacture more raw materials.

It is to move from raw-material manufacturing to pharmaceutical-material technology.

For PLGA, that means controlling drug release rather than simply polymerizing lactide and glycolide.

For Copovidone and HPMCAS, it means enabling poorly soluble molecules to become viable medicines.

For SBE-β-CD, it means solving formulation and solubility limitations.

For biopharmaceutical surfactants, it means protecting complex proteins throughout manufacturing and storage.

For ionizable lipids, it ultimately means enabling nucleic-acid medicines to reach their intracellular target.

That is the direction in which the global pharmaceutical-material industry is moving.

The relevant opportunity for Iran is not to reproduce every material currently sold by established global suppliers.

It is to identify a small number of points in this evolving value chain where existing industrial capabilities can be converted into deep, defensible and exportable pharmaceutical know-how.

*Author: Mehdi Mahdavian Sadr, Vice President of Research and Development, Rahavard Tamin Pharmaceutical Knowledge-Based Company 

Selected References

1. Park, K. (2025). PLGA-based long-acting injectable (LAI) formulations. Journal of Controlled Release, 382, 113758. DOI: 10.1016/j.jconrel.2025.113758.
2. Wang, Y., Otte, A., Park, H., & Park, K. (2025). In vitro-in vivo correlation development for long-acting injectable drug products based on poly(lactide-co-glycolide). Journal of Controlled Release, 377, 186–196.
3. Wan, B., Bao, Q., & Burgess, D. J. (2022). In vitro-in vivo correlation of PLGA microspheres: Effect of polymer source variation and temperature. Journal of Controlled Release, 347, 347–355.
4. Clark, A. G., Wang, R., Qin, Y., et al. (2022). Assessing microstructural critical quality attributes in PLGA microspheres by FIB-SEM analytics. Journal of Controlled Release, 349, 580–591.
5. Otte, A., & Park, K. (2022). Transitioning from a lab-scale PLGA microparticle formulation to pilot-scale manufacturing. Journal of Controlled Release, 348, 841–848.
6. Skidmore, S., et al. (2019). Characterization of branched poly(lactide-co-glycolide) polymers used in injectable, long-acting formulations. Journal of Controlled Release, 304, 75–89.
7. Ogawa, Y., Yamamoto, M., Takada, S., Okada, H., & Shimamoto, T. (1988). Controlled-release of leuprolide acetate from polylactic acid or copoly(lactic/glycolic) acid microcapsules: Influence of molecular weight and copolymer ratio of polymer. Chemical and Pharmaceutical Bulletin, 36(4), 1502–1507.
8. Okada, H. (1997). One- and three-month release injectable microspheres of the LH-RH superagonist leuprorelin acetate. Advanced Drug Delivery Reviews, 28(1), 43–70.
9. U.S. Food and Drug Administration. (2025). FY 2024 GDUFA Science and Research Report: Long-Acting Injectable, Insertable, or Implantable Products.
10. United States Pharmacopeia. DL-Lactide and Glycolide Copolymer Monographs and General Chapter <1059>, Excipient Performance.
11. Moseson, D. E., et al. (2024). Trends in amorphous solid dispersion drug products approved by the U.S. Food and Drug Administration between 2012 and 2023. International Journal of Pharmaceutics: X, 7, 100259.
12. Ramachandran, G., et al. (2025). A review on design rules for formulating amorphous solid dispersions based on drug-polymer interactions in aqueous environment. International Journal of Pharmaceutics, 675, 125541.
13. Tanno, F., Nishiyama, Y., Kokubo, H., & Obara, S. (2004). Evaluation of hypromellose acetate succinate as a carrier in solid dispersions. Drug Development and Industrial Pharmacy.
14. Khunt, D., et al. (2023). Sulfobutylether-β-cyclodextrin: A functional biopolymer for drug delivery applications. Carbohydrate Polymers, 301, 120347.
15. Bollenbach, L., Buske, J., Mäder, K., & Garidel, P. (2022). Poloxamer 188 as surfactant in biological formulations – An alternative for polysorbate 20/80? International Journal of Pharmaceutics, 620, 121706.
16. A pharmaceutical industry survey on exploring polysorbate alternatives in biological drug products: Poloxamer and other surfactants. Journal of Pharmaceutical Sciences, 2025.
17. Felix, M. N., et al. (2025). Polysorbates degrading enzymes in biotherapeutics – a current status and future perspectives.
18. O’Brien Laramy, M., et al. (2025). Chemistry, manufacturing and controls strategies for using novel excipients in lipid nanoparticles. Nature Nanotechnology, 20, 331–344.
19. Boetzel, R., et al. (2023). A Nitrite Excipient Database: A Useful Tool to Support N-Nitrosamine Risk Assessments for Drug Products. Journal of Pharmaceutical Sciences, 112, 1615–1624.
20. U.S. Food and Drug Administration. (2024). Control of Nitrosamine Impurities in Human Drugs: Guidance for Industry.
21. World Health Organization. (2025). WHO Good Manufacturing Practices for Excipients Used in Pharmaceutical Products. WHO Technical Report Series No. 1060, Annex 3.
22. World Health Organization. (2025). WHO Good Practice Considerations for the Prevention and Control of Nitrosamines in Pharmaceutical Products. WHO Technical Report Series No. 1060, Annex 2.
23. Japanese Pharmacopoeia / Pharmaceuticals and Medical Devices Agency. Hypromellose Acetate Succinate Monograph.
24. Swissmedic / AIPS. Sandostatin LAR: Product Information.
25. Takeda Pharmaceutical Company. Development history of sustained-release leuprorelin formulations.